The Discriminative Stimulus Effects of KA 672, a Putative Cognitive Enhancer: Evidence for a 5-HT 1A Component

Abstract

Stimulus control was established in a group of seven rats using a dose of KA 672 [7-methoxy-6-{3-[4-(2-methoxyphenyl)-1-piperazinyl] propoxy}3,4-dimethyl-2H-1-benzopyran-2-one HCl] of 1.0 mg/kg, administered IP, 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 23 sessions was required to reach criterion performance. Subsequently, it was observed that KA 672-induced stimulus control is partially but significantly antagonized by the selective 5-HT 1A antagonist, WAY-100635. Furthermore, KA 672 generalized to the selective 5-HT 1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this generalization was blocked by WAY-100635. Other tests of generalization were conducted with the structural analogs, scoparone, CD-127, and OMPP, as well as with the receptor-selective ligands ketamine, PCP, dizocilpine, prazosin, urapidil, apomorphine, and DTG. Of these drugs only dizocilpine met the criteria for full substitution while an intermediate level of generalization was observed to ketamine, PCP, urapidil, and apomorphine. The present results indicate that KA 672-induced stimulus control is mediated in part by activity at the 5-HT 1A receptor and that behaviorally significant interactions occur as well at PCP/NMDA, dopaminergic, and adrenergic receptors.