Discriminative stimulus effects of m-chlorophenylpiperazine as a model of the role of serotonin receptors in anxiety

Serotonin is known to play a role in anxiety. The roles of serotonin reuptake and 5-HT_1A receptors have been well characterized, but the contribution of other serotonin receptor subtypes is not as clear. 1-(3-Chlorophenyl)-piperazine (mCPP), which binds non-selectively to a wide range of serotonin receptors, has often been used to produce anxiety in humans and in animal models. Because functional assays indicate that mCPP is significantly more potent at 5-HT_2C receptors, it may serve as a tool to investigate the contribution of 5-HT_2C receptors to anxiety. This paper reviews the results of behavioral tests using mCPP, including the drug discrimination assay, to model anxiety. Although the discriminative stimulus effects of mCPP do not seem to be a useful screen for general anxiolytics, they do seem to be useful for characterization of the contribution of 5-HT_1B and 5-HT_2C receptors to the mediation of anxiety-like behaviors.