Serotonergic basis of reward in median raphé of the rat

Miliaressis, Elefthérios

doi:10.1016/0091-3057(77)90204-0

Cited by 34 publications

(10 citation statements)

References 7 publications

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“…1,51,52 At both molecular and systems levels, the brain utilizes 5-HT within cellular cascades and webs comprised of transcription factors, growth factors and other neurotransmitters, as a mediator of integral physiological and psychological functions, including the processing of incentive-motivational stimuli and impulse control. 51,53–56 Acute tryptophan depletion in humans, which temporarily lowers brain 5-HT levels, elevates motor impulsivity 57 and disrupts motivated actions selectively in individuals with high inherent impulsivity. 58 Depletion of 5-HT in the dorsal raphe nucleus causes a robust increase in impulsive action in rodents, 59,60 while elevated 5-HT release in the mPFC positively correlates with motor impulsivity.…”

Section: Resultsmentioning

confidence: 99%

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Anastasio¹,

Stutz

Fink

et al. 2015

ACS Chem. Neurosci.

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A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally-relevant mechanism underlying motor impulsivity.

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Section: Resultsmentioning

confidence: 99%

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Anastasio¹,

Stutz

Fink

et al. 2015

ACS Chem. Neurosci.

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“…Multiple, somewhat distinguishable, facets of reward include hedonic value (`liking'), the organism's motivation to approach and consume rewards (incentive salience; `wanting'), and the learning of predictive associations between the reward and allied internal/external stimuli (drug-associated stimuli) (Berridge, et al, 2009). The activity of 5-HT neurons that innervate limbic-corticostriatal circuit controls the hedonic value of natural rewards (Nakamura, et al, 2008; Ranade and Mainen, 2009) and the motivational aspects of reward evoked by intracranial self-stimulation (Miliaressis, 1977; Simon, et al, 1976; Van der Kooy, et al, 1978). Electrophysiological studies in monkeys suggest that neurons in the DRN encode reward-seeking behaviors, and that DRN 5-HT neurons broadcast reward-related information to the forebrain (Bromberg-Martin, et al, 2010; Inaba, et al, 2013; Miyazaki, et al, 2011a; Miyazaki, et al, 2011b).…”

Section: Cocaine Reward and Serotoninmentioning

confidence: 99%

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

2014

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Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction.

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“…The majority of self-stimulation studies have focused on the medial forebrain bundle, which contains ascending dopaminergic fibers; however, several studies have also shown that stimulation of the raphé nuclei and their vicinity is equally effective (Miliaressis et al, 1975; Miliaressis, 1977; Rompre and Miliaressis, 1985). In addition, some pharmacological experiments using the systemic reduction of 5-HT reported attenuated cocaine-seeking behavior (Tran-Nguyen et al, 1999, 2001).…”

Section: -Ht and The Reward Circuitmentioning

confidence: 99%

The role of the dorsal raphé nucleus in reward-seeking behavior

Nakamura¹

2013

Front. Integr. Neurosci.

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Pharmacological experiments have shown that the modulation of brain serotonin levels has a strong impact on value-based decision making. Anatomical and physiological evidence also revealed that the dorsal raphé nucleus (DRN), a major source of serotonin, and the dopamine system receive common inputs from brain regions associated with appetitive and aversive information processing. The serotonin and dopamine systems also have reciprocal functional influences on each other. However, the specific mechanism by which serotonin affects value-based decision making is not clear. To understand the information carried by the DRN for reward-seeking behavior, we measured single neuron activity in the primate DRN during the performance of saccade tasks to obtain different amounts of a reward. We found that DRN neuronal activity was characterized by tonic modulation that was altered by the expected and received reward value. Consistent reward-dependent modulation across different task periods suggested that DRN activity kept track of the reward value throughout a trial. The DRN was also characterized by modulation of its activity in the opposite direction by different neuronal subgroups, one firing strongly for the prediction and receipt of large rewards, with the other firing strongly for small rewards. Conversely, putative dopamine neurons showed positive phasic responses to reward-indicating cues and the receipt of an unexpected reward amount, which supports the reward prediction error signal hypothesis of dopamine. I suggest that the tonic reward monitoring signal of the DRN, possibly together with its interaction with the dopamine system, reports a continuous level of motivation throughout the performance of a task. Such a signal may provide “reward context” information to the targets of DRN projections, where it may be integrated further with incoming motivationally salient information.

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Serotonergic basis of reward in median raphé of the rat

Cited by 34 publications

References 7 publications

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

The role of the dorsal raphé nucleus in reward-seeking behavior

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Serotonergic basis of reward in median raphé of the rat

Cited by 34 publications

References 7 publications

Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

The role of the dorsal raphé nucleus in reward-seeking behavior

Contact Info

Product

Resources

About

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

Serotonin (5-HT) 5-HT_2A Receptor (5-HT_2AR):5-HT_2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity