title: Influence of nitric oxide on morphine-induced amnesia and interactions with dopaminergic receptor agents.
abstract: The interactions of dopaminergic receptors and nitric oxide (NO) with morphine-induced memory of passive avoidance have been investigated in mice. Pre-training administration of morphine (1, 3 and 5 mg/kg, s.c.) dose-dependently decreased the learning of a one-trial passive avoidance task. Pre-training administration of L-arginine, a nitric oxide precursor (50, 100 and 200 mg/kg, i.p.), alone did not affect memory formation. The drug (100 and 200 mg/kg) decreased significantly amnesia induced by pre-training morphine (5 mg/kg). Pre-training administration of L-NAME (N(G)-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (20 and 30 mg/kg, i.p.), dose-dependently impaired memory formation. In addition, co-pretreatment of different doses of L-NAME (10, 20 and 30 mg/kg) with lower dose of morphine (1 mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Pre-training administration of apomorphine, a dopaminergic receptor agonist (0.25, 0.5 and 1 mg/kg, i.p.), alone also did not affect memory formation, but morphine-induced amnesia was significantly inhibited by pretreatment with apomorphine (0.5 and 1 mg/kg, 5 min, i.p.). On the other hand, the inhibition of morphine-induced amnesia by L-arginine (200 mg/kg, i.p.) was significantly decreased by pretreatment with different doses of dopamine D1 receptor antagonist, SCH 23390 (0.001, 0.01 and 0.1 mg/kg, i.p.) or D2 receptor antagonist, sulpiride (12.5, 25, 50 and 100 mg/kg, i.p.). However, the dopamine receptor antagonists could not affect memory formation by themselves. It may be concluded that the morphine-induced impairment of memory formation can be prevented by nitric oxide donor and, in this effect, dopaminergic mechanism is involved.
authors.affiliation: School of Biology, University College of Science, University of Tehran, Tehran, Iran.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.forename: Rana
authors.initials: R
authors.lastname: Amini
authors.forename: Yassaman
authors.initials: Y
authors.lastname: Rassouli
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009294:Narcotics / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects
chemical_list: D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D009294:Narcotics; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester