Nitric oxide within the ventral tegmental area is involved in mediating morphine reward.
In the present study, the effects of intra-ventral tegmental area injection of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on morphine-induced conditioned place preference in male Wistar rats were investigated. Our data showed that subcutaneous (s.c.) injection of morphine sulphate (0.5-10 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intra-ventral tegmental area administration of a low dose of L-arginine (0.05 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited significant conditioned place preference; however, a higher dose of L-arginine (0.1 microg/rat) reduced the morphine response. Intra-ventral tegmental area administration of L-NAME (0.03 and 0.1 microg/rat) decreased the acquisition of morphine (7.5 mg/kg)-induced place preference. The response to different doses of L-arginine was decreased by L-NAME (0.03 microg/rat). L-Arginine and L-NAME by themselves did not elicit any effect on place conditioning; however, intra-ventral tegmental area administration of L-arginine (0.01-0.1 microg/rat) and a higher dose of L-NAME (0.1 microg/rat) significantly decreased the expression of morphine (7.5 mg/kg)-induced place preference. The attenuation of already established morphine-induced place preference on the test day by L-arginine was inhibited by L-NAME (0.03 microg/rat). The results indicate that NO may be involved in the acquisition and expression of morphine-induced place preference.
Gholami
Azam
A
Department of Biology, Faculty of Science, Tehran University, Tehran, Iran.
Zarrindast
Mohammad Reza
MR
Sahraei
Hedayat
H
Haerri-Rohani
Ali
A
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009294:Narcotics; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester