Yohimbine and serotonergic agonists: Stimulus properties and receptor binding

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Abstract
The present investigation was designed to compare the discriminative stimulus properties of yohimbine and purported agonists at the serotonin (5‐HT)1A receptor. To that end, groups of rats were trained with yohimbine, 8‐OH‐DPAT, and ipsapirone, respectively. Tests of generalization were then conducted, and the interaction between clonidine and yohimbine was examined. Drugs examined behaviorally were also characterized in terms of their relative affinities at the 5‐HT1A, 5‐HT1B, and 5‐HT2 receptors by means of standard radioligand binding techniques. A high degree of generalization was observed between each of the training drugs and in tests of gepirone and buspirone. Comparisons of the behavioral and receptor binding data argue against stimulus control mediated solely by a 5‐HT1A‐based mechanism. The observed pattern of interaction of clonidine with yohimbine in rats trained with the latter drug suggests that clonidine may function as a partial agonist. Whatever the mechanistic basis for the present discrimination data, we are left with the puzzle of why yohimbine, widely regarded as anxiogenic, should share stimulus properties with anxiolytic drugs.