Serotonin and Reward-Related Behavior: Focus on 5-HT2C Receptors

Abstract

AbstractSerotonin has long been known to exert inhibitory and excitatory influences over the activity of dopaminergic neurons. Electrophysiological and neurochemical evidence indicates that the inhibitory effect of 5-HT is mediated predominantly via the 5-HT2C receptor subtype. Given the major role that dopamine plays in reward-related behavior it is not surprising that ligands for 5-HT2C receptors modify this type of behavior. A number of studies from different laboratories have shown that 5-HT receptor agonists consistently alter the behavioral effects of drugs of abuse, most notably cocaine and nicotine. In particular, 5-HT2C agonists reduce the locomotor stimulant, discriminative stimulus properties, and reinforcing effects of cocaine and nicotine. In animals with a previous history of cocaine self-administration, 5-HT2C receptor agonists prevent the reinstatement of drug-seeking behavior induced by reexposure to cocaine, stress, or drug-associated cues. Under some experimental conditions reducing 5-HT2C-mediated transmission through receptor blockade or 5-HT2C receptor gene deletion enhances the effects of cocaine. 5-HT2C receptor agonists reduce other reward-related behaviors including brain stimulation reward, and feeding behavior. Impulsive behavior has been linked to drug abuse and is also reduced by 5-HT2C agonists and enhanced by 5-HT2C antagonists. The overall behavioral profile of 5-HT2C agonists indicates that this class of drug has the potential for use as medication to treat substance abuse and dependence. One 5-HT2C receptor agonist, lorcaserin, is in an advanced stage of clinical testing for obesity. Thus, the opportunity of testing 5-HT2C receptor agonists for their ability to treat drug abuse, drug dependence, and ancillary behaviors such as impulsivity is potentially close at hand.KeywordsNucleus AccumbensConditioned Place PreferenceProgressive Ratio ScheduleImpulsive ActionBrain Stimulation RewardThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.