Du W, Weiss H, Harvey J A
MCP Hahnemann University, Department of Pharmacology and Physiology, Philadelphia, PA 19129, USA.
Psychopharmacology (Berl). 2000 Jun;150(3):264-71. doi: 10.1007/s002130000412.
Previous studies had reported that the nitric oxide (NO) donor, sodium nitroprusside (SNP), retarded and the non-specific NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), enhanced acquisition of classically conditioned responses (CRs). These effects of IV SNP and IP L-NAME on CR acquisition occurred in the absence of any effect on non-associative processes or performance variables and at a time when there were no alterations in blood pressure or heart rate.
In this study, we examined whether the changes in associative learning produced by L-NAME and SNP were due to their central effects on NO content of brain. To this end, we examined the effects of the selective neuronal NOS inhibitors 7-nitroindazole (7-NI) and AR-R 17477 and the effects of central (ICV) administration of the NO donor SNP on learning.
Effects of drugs on CR acquisition were determined during classical conditioning of the rabbit's nictitating membrane (NM) response. Explicitly unpaired presentations of conditioned stimuli (CSs) and unconditioned stimuli (USs) were employed to measure non-associative levels of responding and unconditioned response (UR) topography.
The SC injection of 7-NI and AR-R 17477 significantly enhanced associative learning while ICV administration of SNP significantly retarded learning.
Production of NO within the brain by neuronal NOS normally acts to retard associative learning presumably by decreasing excitability within neuronal circuits involved in the acquisition of the classically conditioned NM reflex.
先前的研究报道，一氧化氮（NO）供体硝普钠（SNP）会延缓经典条件反应（CR）的获得，而非特异性一氧化氮合酶（NOS）抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）则会增强其获得。静脉注射SNP和腹腔注射L-NAME对CR获得的这些影响发生在对非联想过程或行为变量没有任何影响的情况下，且此时血压和心率没有改变。
在本研究中，我们研究了L-NAME和SNP产生的联想学习变化是否归因于它们对脑内NO含量的中枢作用。为此，我们研究了选择性神经元NOS抑制剂7-硝基吲唑（7-NI）和AR-R 17477的作用，以及中枢（脑室内）给予NO供体SNP对学习的影响。
在兔瞬膜（NM）反应的经典条件反射过程中确定药物对CR获得的影响。使用条件刺激（CS）和非条件刺激（US）的明确非配对呈现来测量反应的非联想水平和非条件反应（UR）的特征。
皮下注射7-NI和AR-R 17477显著增强了联想学习，而脑室内给予SNP则显著延缓了学习。
神经元NOS在脑内产生的NO通常通过降低参与经典条件性NM反射获得的神经回路内的兴奋性来延缓联想学习。
