Generalization of the discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone to yohimbine.

Rats were trained with either 8-OH-DPAT (0.2 mg/kg) or ipsapirone (10 mg/kg) versus saline in a 2-lever discrimination task. Tests of generalization were then conducted with yohimbine. All drugs were administered IP 15 min before testing. In 8-OH-DPAT-trained subjects, 85% of the responses following yohimbine (3 mg/kg) were on the drug-appropriate lever. Likewise, yohimbine (6 mg/kg) yielded 86% drug-appropriate responses in ipsapirone-trained rats. Previous studies have provided evidence that both 8-OH-DPAT and ipsapirone have high affinity for 5-HT1A receptors and the anxiolytic-like activity of the latter drug has been attributed to its activity at those receptors. In contrast, yohimbine is an alpha 2 adrenergic antagonist, has negligible affinity for the 5-HT1A receptor, and is generally regarded as being anxiogenic. The present data, which indicate a high degree of similarity between the stimuli induced by yohimbine, 8-OH-DPAT, and ipsapirone, suggest that a re-evaluation of the presumed mechanisms of actions of these drugs is in order.