Influence of intracerebroventricular administration of cannabinergic drugs on morphine state-dependent memory in the step-down passive avoidance test.
The effects of cannabinergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training (0.25, 0.5 and 5 mg/kg) and post-training (5 mg/kg) administration of morphine impaired memory retrieval on the test day. Impairment of memory retrieval by morphine (5 mg/kg) on the test day was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular administration of the cannabinoid CB1/CB2 receptor agonist (WIN55,212-2) (0.75 and 1 microg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. Furthermore, the pre-test intracerebroventricular administration of CB1 receptor antagonist (AM251) (20 and 100 ng/mouse) prevented the restoration of memory by morphine. Pre-training administration of WIN55,212-2 (1 microg/mouse) led to state-dependent learning with impaired memory retrieval on the test day as well, which was reversed by pre-test administration of the drug (0.5, 0.75 and 1 microg/mouse) or morphine (1 and 5 mg/kg). Restoration of impairment induced by WIN55,212-2 was decreased by both the opioid receptor antagonists, naloxone (0.01 microg/mouse) and AM251 (20 and 100 ng/mouse). In conclusion, the improvement of memory retrieval by morphine treatment on the test day seems to be induced, at least in part, by the cannabinoid CB1 receptors.
Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. zrrndst@yahoo.com
Mohammad-Reza
MR
Zarrindast
Katayoun
K
Kangarlu-Haghighi
Azita
A
Khalilzadeh
Soheila
S
Fazli-Tabaei
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D048588:Benzoxazines; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors*
D000701:Analgesics, Opioid; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009270:Naloxone; C103505:AM 251; 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