Klamer Daniel, Pålsson Erik, Wass Caroline, Archer Trevor, Engel Jörgen A, Svensson Lennart
Department of Pharmacology, The Sahlgrenska Academy at Göteborg University, Göteborg University, P.O.B. 431, SE 405-30 Göteborg, Sweden.
Behav Brain Res. 2005 Jun 3;161(1):60-8. doi: 10.1016/j.bbr.2005.01.008. Epub 2005 Feb 16.
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.
潜伏抑制(LI)是一种用于评估精神活性药物潜在的促精神病和抗精神病特性的行为程序。在本研究中,采用条件性味觉厌恶(CTA)程序来研究一氧化氮(NO)合酶抑制剂N(G)-硝基-L-精氨酸甲酯(L-NAME)以及拟精神病药物苯环己哌啶(PCP)和右旋苯丙胺(d-AMP)对LI的影响。在此程序中,发现PCP(2mg/kg)和d-AMP(0.5mg/kg)均能增强LI。d-AMP对LI的影响不太明显,且该药物还会对味觉厌恶条件反射造成轻微干扰。用L-NAME(10mg/kg)预处理可阻断PCP对LI的增强作用,但不能阻断d-AMP的这种作用。L-NAME自身会导致LI减弱。在先前的研究中已表明L-NAME还可阻断PCP的其他行为和生化效应,这些结果以及当前的发现表明,PCP的至少某些效应依赖于NO,并且一些一氧化氮合酶抑制剂可能也具有抗精神病特性。