Analysis of information sources in references of the Wikipedia article "Ödül sistemi" in Turkish language version.
[The striatum] receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al., 2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the [nucleus accumbens] NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a 'go’ signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a 'brake’ to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and Nestler, 2011; Grueter et al., 2013). For example, optogenetic activation of NAc core and shell iMSNs suppressed the development of a cocaine CPP whereas selective ablation of NAc core and shell iMSNs ... enhanced the development and the persistence of an amphetamine CPP (Durieux et al., 2009; Lobo et al., 2010). These findings suggest that iMSNs can bidirectionally modulate drug reward. ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use.
Regions of the basal ganglia, which include the dorsal and ventral striatum, internal and external segments of the globus pallidus, subthalamic nucleus, and dopaminergic cell bodies in the substantia nigra, are highly implicated not only in fine motor control but also in [prefrontal cortex] PFC function.43 Of these regions, the [nucleus accumbens] NAc (described above) and the [dorsal striatum] DS (described below) are most frequently examined with respect to addiction. Thus, only a brief description of the modulatory role of the basal ganglia in addiction-relevant circuits will be mentioned here. The overall output of the basal ganglia is predominantly via the thalamus, which then projects back to the PFC to form cortico-striatal-thalamo-cortical (CSTC) loops. Three CSTC loops are proposed to modulate executive function, action selection, and behavioral inhibition. In the dorsolateral prefrontal circuit, the basal ganglia primarily modulate the identification and selection of goals, including rewards.44 The [orbitofrontal cortex] OFC circuit modulates decision-making and impulsivity, and the anterior cingulate circuit modulates the assessment of consequences.44 These circuits are modulated by dopaminergic inputs from the [ventral tegmental area] VTA to ultimately guide behaviors relevant to addiction, including the persistence and narrowing of the behavioral repertoire toward drug seeking, and continued drug use despite negative consequences.43–45
Here, we show that opioid or orexin stimulations in orbitofrontal cortex and insula causally enhance hedonic “liking” reactions to sweetness and find a third cortical site where the same neurochemical stimulations reduce positive hedonic impact.
For instance, mesolimbic dopamine, probably the most popular brain neurotransmitter candidate for pleasure two decades ago, turns out not to cause pleasure or liking at all. Rather dopamine more selectively mediates a motivational process of incentive salience, which is a mechanism for wanting rewards but not for liking them .... Rather opioid stimulation has the special capacity to enhance liking only if the stimulation occurs within an anatomical hotspot
Rewards in operant conditioning are positive reinforcers. ... Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of several reward functions. ... Rewards are attractive. They are motivating and make us exert an effort. ... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior. ... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward. ... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory) ... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses (FIGURE 1, middle). The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning) ... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components (FIGURE 1, right). This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism’s survival and reproduction, whereas all other components are only supportive of these functions. ... Rewards can also be intrinsic to behavior (31, 546, 547). They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards. ... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward. ... These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research (471) and strongly support the learning and approach generating functions of reward.
Importantly, we found evidence of increased activity in the direct pathway; both intracellular changes in the expression of the plasticity marker pERK and AMPA/NMDA ratios evoked by stimulating cortical afferents were increased in the D1-direct pathway neurons. In contrast, D2 neurons showed an opposing change in plasticity; stimulation of cortical afferents reduced AMPA/NMDA ratios on those neurons (Shan et al., 2014).
Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers 9 Ağustos 2021 tarihinde Wayback Machine sitesinde arşivlendi."
Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.Figure 4: Epigenetic basis of drug regulation of gene expression 8 Mart 2021 tarihinde Wayback Machine sitesinde arşivlendi.
They also provide a separate assessment of the consummatory anhedonia (reduced experience of pleasure derived from ongoing enjoyable activities) and anticipatory anhedonia (reduced ability to anticipate future pleasure). In fact, the former one seems to be relatively intact in schizophrenia, whereas the latter one seems to be impaired [32 – 34]. However, discrepant data have also been reported [35].
Listening to pleasurable music is often accompanied by measurable bodily reactions such as goose bumps or shivers down the spine, commonly called “chills” or “frissons.” ... Overall, our results straightforwardly revealed that pharmacological interventions bidirectionally modulated the reward responses elicited by music. In particular, we found that risperidone impaired participants’ ability to experience musical pleasure, whereas levodopa enhanced it. ... Here, in contrast, studying responses to abstract rewards in human subjects, we show that manipulation of dopaminergic transmission affects both the pleasure (i.e., amount of time reporting chills and emotional arousal measured by EDA) and the motivational components of musical reward (money willing to spend). These findings suggest that dopaminergic signaling is a sine qua non condition not only for motivational responses, as has been shown with primary and secondary rewards, but also for hedonic reactions to music. This result supports recent findings showing that dopamine also mediates the perceived pleasantness attained by other types of abstract rewards (37) and challenges previous findings in animal models on primary rewards, such as food (42, 43).
In a pharmacological study published in PNAS, Ferreri et al. (1) present evidence that enhancing or inhibiting dopamine signaling using levodopa or risperidone modulates the pleasure experienced while listening to music. ... In a final salvo to establish not only the correlational but also the causal implication of dopamine in musical pleasure, the authors have turned to directly manipulating dopaminergic signaling in the striatum, first by applying excitatory and inhibitory transcranial magnetic stimulation over their participants’ left dorsolateral prefrontal cortex, a region known to modulate striatal function (5), and finally, in the current study, by administrating pharmaceutical agents able to alter dopamine synaptic availability (1), both of which influenced perceived pleasure, physiological measures of arousal, and the monetary value assigned to music in the predicted direction. ... While the question of the musical expression of emotion has a long history of investigation, including in PNAS (6), and the 1990s psychophysiological strand of research had already established that musical pleasure could activate the autonomic nervous system (7), the authors’ demonstration of the implication of the reward system in musical emotions was taken as inaugural proof that these were veridical emotions whose study has full legitimacy to inform the neurobiology of our everyday cognitive, social, and affective functions (8). Incidentally, this line of work, culminating in the article by Ferreri et al. (1), has plausibly done more to attract research funding for the field of music sciences than any other in this community. The evidence of Ferreri et al. (1) provides the latest support for a compelling neurobiological model in which musical pleasure arises from the interaction of ancient reward/valuation systems (striatal–limbic–paralimbic) with more phylogenetically advanced perception/predictions systems (temporofrontal).
Listening to pleasurable music is often accompanied by measurable bodily reactions such as goose bumps or shivers down the spine, commonly called “chills” or “frissons.” ... Overall, our results straightforwardly revealed that pharmacological interventions bidirectionally modulated the reward responses elicited by music. In particular, we found that risperidone impaired participants’ ability to experience musical pleasure, whereas levodopa enhanced it. ... Here, in contrast, studying responses to abstract rewards in human subjects, we show that manipulation of dopaminergic transmission affects both the pleasure (i.e., amount of time reporting chills and emotional arousal measured by EDA) and the motivational components of musical reward (money willing to spend). These findings suggest that dopaminergic signaling is a sine qua non condition not only for motivational responses, as has been shown with primary and secondary rewards, but also for hedonic reactions to music. This result supports recent findings showing that dopamine also mediates the perceived pleasantness attained by other types of abstract rewards (37) and challenges previous findings in animal models on primary rewards, such as food (42, 43).
[The striatum] receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al., 2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the [nucleus accumbens] NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a 'go’ signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a 'brake’ to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and Nestler, 2011; Grueter et al., 2013). For example, optogenetic activation of NAc core and shell iMSNs suppressed the development of a cocaine CPP whereas selective ablation of NAc core and shell iMSNs ... enhanced the development and the persistence of an amphetamine CPP (Durieux et al., 2009; Lobo et al., 2010). These findings suggest that iMSNs can bidirectionally modulate drug reward. ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use.
Regions of the basal ganglia, which include the dorsal and ventral striatum, internal and external segments of the globus pallidus, subthalamic nucleus, and dopaminergic cell bodies in the substantia nigra, are highly implicated not only in fine motor control but also in [prefrontal cortex] PFC function.43 Of these regions, the [nucleus accumbens] NAc (described above) and the [dorsal striatum] DS (described below) are most frequently examined with respect to addiction. Thus, only a brief description of the modulatory role of the basal ganglia in addiction-relevant circuits will be mentioned here. The overall output of the basal ganglia is predominantly via the thalamus, which then projects back to the PFC to form cortico-striatal-thalamo-cortical (CSTC) loops. Three CSTC loops are proposed to modulate executive function, action selection, and behavioral inhibition. In the dorsolateral prefrontal circuit, the basal ganglia primarily modulate the identification and selection of goals, including rewards.44 The [orbitofrontal cortex] OFC circuit modulates decision-making and impulsivity, and the anterior cingulate circuit modulates the assessment of consequences.44 These circuits are modulated by dopaminergic inputs from the [ventral tegmental area] VTA to ultimately guide behaviors relevant to addiction, including the persistence and narrowing of the behavioral repertoire toward drug seeking, and continued drug use despite negative consequences.43–45
Here, we show that opioid or orexin stimulations in orbitofrontal cortex and insula causally enhance hedonic “liking” reactions to sweetness and find a third cortical site where the same neurochemical stimulations reduce positive hedonic impact.
For instance, mesolimbic dopamine, probably the most popular brain neurotransmitter candidate for pleasure two decades ago, turns out not to cause pleasure or liking at all. Rather dopamine more selectively mediates a motivational process of incentive salience, which is a mechanism for wanting rewards but not for liking them .... Rather opioid stimulation has the special capacity to enhance liking only if the stimulation occurs within an anatomical hotspot
Rewards in operant conditioning are positive reinforcers. ... Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of several reward functions. ... Rewards are attractive. They are motivating and make us exert an effort. ... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior. ... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward. ... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory) ... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses (FIGURE 1, middle). The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning) ... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components (FIGURE 1, right). This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism’s survival and reproduction, whereas all other components are only supportive of these functions. ... Rewards can also be intrinsic to behavior (31, 546, 547). They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards. ... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward. ... These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research (471) and strongly support the learning and approach generating functions of reward.
Importantly, we found evidence of increased activity in the direct pathway; both intracellular changes in the expression of the plasticity marker pERK and AMPA/NMDA ratios evoked by stimulating cortical afferents were increased in the D1-direct pathway neurons. In contrast, D2 neurons showed an opposing change in plasticity; stimulation of cortical afferents reduced AMPA/NMDA ratios on those neurons (Shan et al., 2014).
Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers 9 Ağustos 2021 tarihinde Wayback Machine sitesinde arşivlendi."
For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.Figure 4: Epigenetic basis of drug regulation of gene expression 8 Mart 2021 tarihinde Wayback Machine sitesinde arşivlendi.
They also provide a separate assessment of the consummatory anhedonia (reduced experience of pleasure derived from ongoing enjoyable activities) and anticipatory anhedonia (reduced ability to anticipate future pleasure). In fact, the former one seems to be relatively intact in schizophrenia, whereas the latter one seems to be impaired [32 – 34]. However, discrepant data have also been reported [35].
Listening to pleasurable music is often accompanied by measurable bodily reactions such as goose bumps or shivers down the spine, commonly called “chills” or “frissons.” ... Overall, our results straightforwardly revealed that pharmacological interventions bidirectionally modulated the reward responses elicited by music. In particular, we found that risperidone impaired participants’ ability to experience musical pleasure, whereas levodopa enhanced it. ... Here, in contrast, studying responses to abstract rewards in human subjects, we show that manipulation of dopaminergic transmission affects both the pleasure (i.e., amount of time reporting chills and emotional arousal measured by EDA) and the motivational components of musical reward (money willing to spend). These findings suggest that dopaminergic signaling is a sine qua non condition not only for motivational responses, as has been shown with primary and secondary rewards, but also for hedonic reactions to music. This result supports recent findings showing that dopamine also mediates the perceived pleasantness attained by other types of abstract rewards (37) and challenges previous findings in animal models on primary rewards, such as food (42, 43).
In a pharmacological study published in PNAS, Ferreri et al. (1) present evidence that enhancing or inhibiting dopamine signaling using levodopa or risperidone modulates the pleasure experienced while listening to music. ... In a final salvo to establish not only the correlational but also the causal implication of dopamine in musical pleasure, the authors have turned to directly manipulating dopaminergic signaling in the striatum, first by applying excitatory and inhibitory transcranial magnetic stimulation over their participants’ left dorsolateral prefrontal cortex, a region known to modulate striatal function (5), and finally, in the current study, by administrating pharmaceutical agents able to alter dopamine synaptic availability (1), both of which influenced perceived pleasure, physiological measures of arousal, and the monetary value assigned to music in the predicted direction. ... While the question of the musical expression of emotion has a long history of investigation, including in PNAS (6), and the 1990s psychophysiological strand of research had already established that musical pleasure could activate the autonomic nervous system (7), the authors’ demonstration of the implication of the reward system in musical emotions was taken as inaugural proof that these were veridical emotions whose study has full legitimacy to inform the neurobiology of our everyday cognitive, social, and affective functions (8). Incidentally, this line of work, culminating in the article by Ferreri et al. (1), has plausibly done more to attract research funding for the field of music sciences than any other in this community. The evidence of Ferreri et al. (1) provides the latest support for a compelling neurobiological model in which musical pleasure arises from the interaction of ancient reward/valuation systems (striatal–limbic–paralimbic) with more phylogenetically advanced perception/predictions systems (temporofrontal).
Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers 9 Ağustos 2021 tarihinde Wayback Machine sitesinde arşivlendi."
ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.Figure 4: Epigenetic basis of drug regulation of gene expression 8 Mart 2021 tarihinde Wayback Machine sitesinde arşivlendi.
