The Role of 5-HT3 Receptors in Drug Abuse and Pharmacotherapy

[Chip (OP)]

source: https://www.researchgate.net/publication/23763083_The_Role_of_5-HT3_Receptors_in_Drug_Abuse_and_as_a_Target_for_Pharmacotherapy

The Role of 5-HT3 Receptors in Drug Abuse and as a Target for Pharmacotherapy

Abstract:

Alcohol and drug abuse continue to be a major public health problem in the United States and other industrialized nations. Extensive preclinical research indicates the mesolimbic^Wiki dopamine (DA) pathway and associated regions mediate the rewarding and reinforcing effects of drugs of abuse and natural rewards, such as food and sex.

The serotonergic (5-HT) system, in concert with others neurotransmitter systems, plays a key role in modulating neuronal systems within the mesolimbic pathway. A substantial portion of this modulation is mediated by activity at the 5-HT3 receptor.

The 5-HT3 receptor is unique among the 5-HT receptors in that it directly gates an ion channel inducing rapid depolarization that, in turn, causes the release of neurotransmitters and/or peptides.

Preclinical findings indicate that antagonism of the 5-HT3 receptor in the ventral tegmental area, nucleus accumbens or amygdala reduces alcohol self-administration and/or alcohol-associated effects. Less is known about the effects of 5-HT3 receptor activity on the self-administration of other drugs of abuse or their associated effects.

Clinical findings parallel the preclinical findings such that antagonism of the 5-HT3 receptor reduces alcohol consumption and some of its subjective effects.

This review provides an overview of the structure, function, and pharmacology of 5-HT3 receptors, the role of these receptors in regulating DA neurotransmission in mesolimbic brain areas, and discusses data from animal and human studies implicating 5-HT3 receptors as targets for the development of new pharmacological agents to treat addictions.