Antagonism of the stimulus effects of yohimbine and 8-hydroxydipropylaminotetralin.

Stimulus control was established in rats using either 8-hydroxy-2-[di-n-propylamino]tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg). Tests were then conducted with purported antagonists at 5-hydroxytryptamine1A (5-HT1A) receptors. Drugs studied were NAN-190, [+/-]-pindolol, and [-]-alprenolol. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2-adrenoceptors by means of radioligand binding techniques. None of the antagonists tested provided complete blockade of the stimulus effects of either DPAT or yohimbine. However, [+/-]-pindolol produced a statistically significant intermediate degree of antagonism of both DPAT and yohimbine. The affinities of DPAT, yohimbine, and NAN-190 for the 5-HT1A and alpha 2-adrenergic receptors, respectively, were sufficiently high to lead to some ambiguity of interpretation of the behavioral data. However, the results with [+/-]-pindolol, which has high affinity for the 5-HT1A receptor (34 nM) and negligible affinity for the alpha 2-adrenoceptor (24,600 nM), indicate that a significant component of yohimbine-induced stimulus control is mediated by the 5-HT1A receptor.