Antagonism of the nitric oxide synthase inhibitor, L-NAME, of the effects of phencyclidine on latent inhibition in taste aversion conditioning.
Latent inhibition (LI) is a behavioural procedure used to evaluate the potential propsychotic and antipsychotic properties of psychoactive drugs. In the present study, a conditioned taste aversion (CTA) procedure was used to investigate the effects of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), and the psychotomimetic drugs, phencyclidine (PCP) and d-amphetamine (d-AMP) on LI. PCP (2 mg/kg) and d-AMP (0.5 mg/kg) were both found to enhance LI in this procedure. The effect of d-AMP on LI was less pronounced and this drug also caused a weak disruption of taste aversion conditioning. Pretreatment with L-NAME (10 mg/kg) blocked the LI enhancing effect of PCP on LI but not that of d-AMP. L-NAME by itself caused an attenuation of LI. L-NAME has been shown to block also other behavioural and biochemical effects of PCP in previous studies and these results and the present findings suggest that at least some of the effects PCP are dependent on NO and possibly also that some NOS inhibitors may exert antipsychotic properties.
Klamer
Daniel
D
Department of Pharmacology, The Sahlgrenska Academy at Göteborg University, Göteborg University, P.O.B. 431, SE 405-30 Göteborg, Sweden.
Pålsson
Erik
E
Wass
Caroline
C
Archer
Trevor
T
Engel
Jörgen A
JA
Svensson
Lennart
L
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007266:Inhibition, Psychological; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013649:Taste / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D010622:Phencyclidine; D003913:Dextroamphetamine; D019331:NG-Nitroarginine Methyl Ester