THE DISCRIMINATIVE STIMULUS EFFECTS OF KA-672, A PUTATIVE COGNITIVE ENHANCER - EVIDENCE FOR A 5-HT1A COMPONENT

Stimulus control was established in a group of seven rats using a dose of KA 672 razinyl]propoxy)3,4-dimethyl-2H-1-benzopyran-2-one HCl] of 1.0 mg/kg, administered IF, 15 min before training. A two-lever operan t 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 response s were on the appropriate lever, a mean of 23 sessions was required to reach criterion performance. Subsequently, it was observed that KA 67 2-induced stimulus control is partially but significantly antagonized by the selective 5-HT1A antagonist, WAY-100635. Furthermore, KA 672 ge neralized to the selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetr alin [8-OH-DPAT], and this generalization was blocked by WAY-100635. O ther tests of generalization were conducted with the structural analog s, 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 sub stitution while an intermediate level of generalization was observed t o ketamine, PCP, urapidil, and apomorphine. The present results indica te that KA 672-induced stimulus control is mediated in part by activit y at the 5-HT1A receptor and that behaviorally significant interaction s occur as well at PCP/NMDA, dopaminergic, and adrenergic receptors. ( C) 1998 Elsevier Science Inc.