title: Central amygdala nicotinic and 5-HT1A receptors mediate the reversal effect of nicotine and MDMA on morphine-induced amnesia.
abstract: The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In addition, pre-test intra-CeA injection of MDMA (1-2-μg/rat) with an ineffective dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the interactive effect of the drugs on memory formation. It should be noted that that pre-test intra-CeA injection of 2-μg/rat of MDMA by itself produced amnesia. Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor antagonist (1-2-μg/rat) or (S)-WAY 100135 (0.25-1-μg/rat), a selective 5-HT1A receptor antagonist inhibited the improvement of morphine-induced amnesia which was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had no effect on morphine-induced amnesia. Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.
authors: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors: F
authors: F
authors: Tirgar
authors: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran. Electronic address: rezayof@khayam.ut.ac.ir.
authors: A
authors: A
authors: Rezayof
authors: Department of Neuroscience, School of Advanced Technologies in Medicine and Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
authors: M-R
authors: MR
authors: Zarrindast
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D009294:Narcotics; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010879:Piperazines; D011978:Receptors, Nicotinic; D058829:Serotonin 5-HT1 Receptor Antagonists; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: cholinergic and serotonergic systems; drugs of abuse; memory retrieval; rat(s)