title: Influence of pre-exposure to morphine on cannabinoid-induced impairment of spatial memory in male rats.
abstract: In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahmandfar
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
authors.forename: Nasser
authors.initials: N
authors.lastname: Naghdi
authors.forename: Samira
authors.initials: S
authors.lastname: Choopani
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000009:adverse effects*; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D009020:Morphine / Q000494:pharmacology*; D009025:Morpholines / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009281:Naphthalenes / Q000009:adverse effects*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000009:adverse effects*; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology; D013647:Task Performance and Analysis; D013997:Time Factors; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; D009294:Narcotics; D011619:Psychotropic Drugs; D009270:Naloxone; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine
keywords: Acquisition; Cannabinoids; Dorsal Hippocampus; Opioids; Rat; Spatial memory