Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT1A receptors

1 Pretraining administration of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH -DPAT 0.1 mg kg(-1)), a 5-HT1A receptor agonist, or buspirone (1 mg kg(-1)) , a 5-HT1A receptor partial agonist, markedly impaired passive avoidance re tention in rats 24 h later. The effect of 8-OH-DPAT was prevented by the 5- HT1A receptor antagonists, NAN-190 and WAY-100635, at doses without any int rinsic effect. 2 N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ 10 mg kg(-1)), an al kylating agent that inactivates different G-protein coupled receptors, impa ired retention performance when given 48 h pretraining. The disruptive effe ct of EEDQ was reversed by 8-OH-DPAT or buspirone, given 30 min before trai ning. 3 Non-specific actions did not account for 8-OH-DPAT-induced reversal of th e EEDQ effect since no significant difference in locomotor activity or in p ain threshold was found between rats receiving EEDQ or EEDQ + 8-OH-DPAT. 4 When NAN-190 (1 mg kg(-1)) or WAY-100635 (0.5 mg kg(-1)) were given befor e 8-OH-DPAT to EEDQ-pretreated animals, the reversal by 8-OH-DPAT of EEDQ-i nduced retention impairment was still more pronounced. However, no EEDQ rev ersal by 8-OH-DPAT was found when 5-HT1A receptors were protected by WAY-10 0635 (10 mg kg(-1)) 30 min before EEDQ. 5 In the hippocampus of EEDQ-treated rats, 5-HT7 receptors were less inacti vated than 5-HT1A receptors and significant increases were found in 5-HT1A but not in 5-HT7 receptor mRNA levels. Ritanserin and methiothepin (10 mg k g(-1) each), antagonists with higher affinity at 5-HT7 than at 5-HT1A recep tors, prevented the retention impairment induced by EEDQ but did not signif icantly protect against 5-HT7 receptor inactivation. 6 The results indicate that the facilitatory effect of 8-OH-DPAT is not med iated through 5-HT1A receptors and suggest that other 8-OH-DPAT-sensitive r eceptors could be involved in the dual effect of 8-OH-DPAT on passive avoid ance performance in rats.