Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine

  title={Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine},
  author={Vicky Katsidoni and Kalliopi Apazoglou and George E. Panagis},
RationaleThe serotonin 5-HT2A and 5-HT2C receptors, which are found in abundance in the mesolimbocortical dopaminergic system, appear to modulate the behavioral effects of cocaine.ObjectivesThe present series of studies set out to investigate the role of 5-HT2A and 5-HT2C receptors on brain reward and on the reward-facilitating effect of cocaine and localize the neural substrates within the mesolimbocortical dopaminergic system that are responsible for these effects.MethodsMale Sprague-Dawley… 

5-HT2A receptors modulate dopamine D2-mediated maternal effects

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It is argued that activation of 5-HT2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms and providing a potential reason for the non-addictive nature of classic hallucinogens.

Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats.

Evaluated LSD, mescaline, and psilocybin effects on intracranial self-stimulation (ICSS) suggest weak expression of abuse-related effects by 5-HT2A agonist hallucinogens and provide supportive evidence for therapeutic effects of repeated LSD dosing to attenuate KOR-mediated depressant effects but not abuse potential of psychostimulants.

Cannabidiol inhibits the reward‐facilitating effect of morphine: involvement of 5‐HT1A receptors in the dorsal raphe nucleus

The findings indicate that cannabidiol does not exhibit reinforcing properties in the ICSS paradigm at any of the doses tested, while it decreases the reward‐facilitating effects of morphine, while these effects were mediated by activation of 5‐HT1A receptors in the dorsal raphe.

Serotonin 5-HT2 Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

The present review will focus on the role of serotonin (5-HT; 5-hydroxytryptamine) neurotransmission in the neuropharmacology of cocaine and related abused stimulants and proposes new approaches to guide targeted development of serotonergic ligands for the treatment of cocaine use disorder.



Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine

Effects of systemic and intra-nucleus accumbens 5-HT2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats

The results suggest that 5-HT2C receptors play an inhibitory role in regulating reward-related behaviour while 5- HT2C receptor activation in the NAc shell did not appear to influence VTA ICSS behaviour under the present experimental conditions.

Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of Serotonin2C (5-HT2C) Receptors in Rat Prefrontal Cortex

The data indicate that the PFC is a brain site at which the 5-HT2CR exerts an inhibitory control over the hyperactive and discriminative stimulus effects of cocaine known to be dependent upon activation of the DA mesoaccumbens circuit.

Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats

Analysis of the role of the 5-HT2R subtypes in the discriminative stimulus effects of cocaine indicates oppositional influence of 4-hydroxyphenyl)-1(2-fluorophenyl)-3-hydroxytryptamine-N′-(3-methyl-5-isothiazolyl)-2(E)-propene and 5- HT2CR may be important in modulating the subjectiveeffects of cocaine in humans.

Opposing Roles for 5-HT2A and 5-HT2C Receptors in the Nucleus Accumbens on Inhibitory Response Control in the 5-Choice Serial Reaction Time Task

The results suggest that the NAc, but not the PL or IL, is implicated in the mediation of the effects of M100907 and SB242084 on inhibitory response control during baseline 5CSRTT performance.

The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of obsessive-compulsive disorder.

The results of these experiments suggest that blockade of 5-HT2Creceptors may have an anti-compulsive effect in OCD patients, and that this effect may be mediated by5- HT2C receptors within the orbitofrontal cortex.

Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence.

A number of selective 5-HT2 R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.

Serotonin and psychostimulant addiction: Focus on 5-HT1A-receptors

Differential Regulation of the Mesoaccumbens Dopamine Circuit by Serotonin2C Receptors in the Ventral Tegmental Area and the Nucleus Accumbens: An In Vivo Microdialysis Study with Cocaine

The idea that the overall action of central 5-HT2CRs on accumbal DA output is dependent, at least in part, on the functional balance between different 5- HT2CR populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc) is supported.

Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking behavior in rats.

  • M. Filip
  • Biology, Psychology
    Pharmacological reports : PR
  • 2005
The findings indicate that 5- HT(2A) and 5-HT(2C) receptors are not significant to cocaine rewarding effects, however, they show the importance of the 5-ht( 2A) receptors (but not 5-Hat(2 C) receptors) in cocaine-priming- and cue-provoked reinstatement, since drugs that reduce cocaine seeking also alleviate cocaine craving.