Abstract
Stimulus control was established in rats trained to discriminate either 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg) from saline. Tests of generalization were then conducted with a group of drugs thought to act via the 5-hydroxytryptamine1A (5-HT1A) receptor and a group of drugs thought to act as antagonists at alpha 2 adrenoceptors. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2 adrenoceptors by means of radioligand binding techniques. It was observed that the stimulus effects of DPAT generalized fully to those of the alpha 2-adrenoceptor antagonists, yohimbine, rauwolscine and L-657,743, but not to idazoxan or atipamezole. The dissociation constants (Kd, nM) of the alpha 2-adrenoceptor antagonists at the 5-HT1A receptor were 74, 52, 80, 199 and 13,000, respectively. Thus, the discrimination data are explicable in terms of a direct action of yohimbine and some other alpha 2 adrenoceptor antagonists upon 5-HT1A receptors. In yohimbine-trained rats, full generalization to DPAT, flesinoxan and tandospirone was observed. In light of the negligible affinity of flesinoxan and tandospirone for the alpha 2 adrenoceptor (9000 and 8800 nM, respectively), and high affinity for the 5-HT1A receptor (0.3 and 43 nM, respectively), a mechanism mediated by the latter site is suggested. We would emphasize two implications of the present study. First, the present data suggest that rats trained with yohimbine as a discriminative stimulus generalize to drugs with minimal affinity for the alpha 2 adrenoceptor but with high affinity for 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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