title: The role of the nitric oxide (NO) pathway in the discriminative stimuli of amphetamine and cocaine.
abstract: To examine the role of the nitric oxide (NO) pathway in the stimulus effects induced by some psychostimulants, separate groups of rats were trained to discriminate between amphetamine (AMPH; 0.5 mg/kg) and saline, or cocaine (COC; 5 mg/kg) and saline using a standard two-lever operant procedure. Substitution studies showed that AMPH and COC generalized for the training drugs in a dose-dependent manner, their ED50, values being 0.1 mg/kg and 1.2 mg/kg, respectively. The dose-response function of both those psychostimulants did not change in the course of the experiment. Moreover, AMPH and COC induced cross-substitution effects towards each other. Successive combination tests demonstrated that injection of a fixed dose of the NO synthase (NOS) inhibitor 7-nitro indazole (7-NI; 25 mg/kg) plus different doses of AMPH or COC resulted in a leftward shift in the dose-response curves of those psychostimulants and a decrease in their ED50 values. On the other hand, pretreatment with the NO donor molsidomine (MOL), injected in a fixed dose of 100 mg/kg before AMPH and COC, shifted the dose-response curves of the psychostimulants to the right and increased their ED50 values. Our results indicate that NO plays an inhibitory role in the dopamine (DA)-evoked discrimination effects of AMPH and COC in rats.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors.forename: M
authors.initials: M
authors.lastname: Filip
authors.forename: E
authors.initials: E
authors.lastname: Przegaliński
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D007191:Indazoles; D009294:Narcotics; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000661:Amphetamine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D003042:Cocaine; C080122:7-nitroindazole