title: Nicotinic acetylcholine receptors of the ventral tegmental area are involved in mediating morphine-state-dependent learning.
abstract: In the present study, the possible role of nicotinic acetylcholine (nACh) receptors of the ventral tegmental area (VTA) on morphine-state-dependent learning was studied in adult male Wistar rats. As a model of memory, a step-through type passive avoidance task was used. All animals were bilaterally implanted with chronic cannulae in the VTA, trained using a 1mA foot shock, and tested 24h after training to measure step-through latency. Post-training subcutaneous (s.c.) injection of morphine (0.5-5mg/kg) dose-dependently reduced the step-through latency, showing morphine-induced amnesia. Amnesia induced by post-training morphine was significantly reversed by pre-test administration of morphine (2.5-5mg/kg, s.c.) and induced morphine-state-dependent learning. Pre-test injection of nicotine (0.25-1microg/rat) into the VTA plus an ineffective dose of morphine (0.5mg/kg) significantly restored the memory retrieval. It should be noted that pre-test intra-VTA injection of the same doses of nicotine (0.25-1microg/rat) alone cannot affect memory retention. Furthermore, pre-test intra-VTA injection of the nicotinic acetylcholine receptor antagonist, mecamylamine (1-3microg/rat) 5min before the administration of morphine (5mg/kg, s.c.) dose-dependently inhibited morphine-state-dependent learning. Pre-test injection of the higher dose of mecamylamine (3microg/rat) into the VTA by itself decreased the step-through latency and induced amnesia. On the other hand, mecamylamine (0.5 and 1microg/rat, intra-VTA) reversed the effect of nicotine on morphine response. The results indicate that nACh receptors in the VTA participate in the modulation of morphine-induced recovery of memory, on the test day.
authors.affiliation: Department of Animal Bioliogy, School of Biology, College of Science, University of Tehran, P. O. Box 4155-6455, Tehran, Iran. rezayof@khayam.ut.ac.ir
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.forename: Niloufar
authors.initials: N
authors.lastname: Darbandi
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000503:physiopathology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine