The 5-HT1B Receptor: Behavioral Implications

5-HT1B receptors are expressed throughout the mammalian central nervous system. These receptors are located in the axon terminals of both serotonergic and nonserotonergic neurons, where they act as inhibitory autoreceptors or heteroreceptors, respectively. 5-HT1B receptors inhibit the release of a range of neurotransmitters, including serotonin, GABA, acetylcholine, and glutamate. These receptors have been difficult to study because of the diversity of their cellular localization and the absence of highly selective agonists and antagonists. There has been accumulating evidence, however, that 5-HT1B receptors modulate drug reinforcement, stress sensitivity, mood, anxiety, and aggression. The general results of a number of studies suggest that reduced 5-HT1B heteroreceptor activity may increase impulsive behaviors, whereas reduced 5-HT1B autoreceptor activity may have an antidepressant-like effect. This review focuses on the evidence from animal studies and human genetics that suggest that 5-HT1B receptors may be involved in the mechanism of action of antidepressants and may become important targets of drug therapy in the future.