Effects of nitric oxide synthase inhibitors on cocaine sensitization.
Behavioral sensitization to cocaine was tested for in rats pretreated with a nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) or 7-nitro indazole (7-NI). A 5-day pre-exposure to once daily cocaine (15 mg/kg, i.p.) injections yielded sensitization to cocaine (15 mg/kg)-induced behavioral activation. Pretreatment injections of L-NAME (100 mg/kg) or 7-NI (30 mg/kg), administered 30 min before each cocaine pre-exposure injection, acutely inhibited cocaine-induced behavioral activation. No sensitization was found after L-NAME pretreatment in a protocol with a 3-day withdrawal between pre-exposure and test cocaine injections. With a 10-day withdrawal period, cocaine sensitization was prevented by L-NAME or 7-NI pretreatment. These results after a 10-day withdrawal are unlikely to arise from deficient brain NO synthase activity on the test day. Instead, these findings suggest a role for NO in mechanisms underlying the development of cocaine sensitization. We conclude that NO participates in both the development of sensitization as well as the expression of cocaine-induced behavior in previously drug-naive animals.
Haracz
J L
JL
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
MacDonall
J S
JS
Sircar
R
R
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007191:Indazoles; D009294:Narcotics; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D003042:Cocaine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester