Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT(1A) receptors.
1. Pretraining administration of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT 0.1 mg kg(-1)), a 5-HT(1A) receptor agonist, or buspirone (1 mg kg(-1)), a 5-HT(1A) receptor partial agonist, markedly impaired passive avoidance retention in rats 24 h later. The effect of 8-OH-DPAT was prevented by the 5-HT(1A) receptor antagonists, NAN-190 and WAY-100635, at doses without any intrinsic effect. 2. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ 10 mg kg(-1)), an alkylating agent that inactivates different G-protein coupled receptors, impaired retention performance when given 48 h pretraining. The disruptive effect of EEDQ was reversed by 8-OH-DPAT or buspirone, given 30 min before training. 3. Non-specific actions did not account for 8-OH-DPAT-induced reversal of the EEDQ effect since no significant difference in locomotor activity or in pain 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 before 8-OH-DPAT to EEDQ-pretreated animals, the reversal by 8-OH-DPAT of EEDQ-induced retention impairment was still more pronounced. However, no EEDQ reversal by 8-OH-DPAT was found when 5-HT(1A) receptors were protected by WAY-100635 (10 mg kg(-1)) 30 min before EEDQ. 5. In the hippocampus of EEDQ-treated rats, 5-HT(7) receptors were less inactivated than 5-HT(1A) receptors and significant increases were found in 5-HT(1A) but not in 5-HT(7) receptor mRNA levels. Ritanserin and methiothepin (10 mg kg(-1) each), antagonists with higher affinity at 5-HT(7) than at 5-HT(1A) receptors, prevented the retention impairment induced by EEDQ but did not significantly protect against 5-HT(7) receptor inactivation. 6. The results indicate that the facilitatory effect of 8-OH-DPAT is not mediated through 5-HT(1A) receptors and suggest that other 8-OH-DPAT-sensitive receptors could be involved in the dual effect of 8-OH-DPAT on passive avoidance performance in rats.
Otano
A
A
Department of Pharmacology, School of Medicine, University of Navarra, Aptdo. 177, 31080-Pamplona, Spain.
García-Osta
A
A
Ballaz
S
S
Frechilla
D
D
Del Río
J
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000477:Alkylating Agents; D011804:Quinolines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; C000470:EEDQ; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin