NEUROPROTECTIVE EFFECT OF SODIUM NITROPRUSSIDE INTRANASAL ADMINISTRATION ON FUNCTIONAL ACTIVITY OF THE BRAIN AND ANXIETY OF RATS WITH ALCOHOL DEPENDENCE

Abstract

Introduction. Disturbances of the molecular nitrosergic mechanisms of brain activity regulation underlie the reduction of brain protective functions under alcohol dependence. However, development of pathogenetically substantiated approaches to the correction of nitrogen oxide (NO) imbalance in the structures of the limbico-neocortical system of the brain (LNCSB) remains insufficient. Objective. To study the effect of intranasal sodium nitroprusside (SNP) administration on anxiety, electrical activity of the LNCSB and NO content in the hippocampus, hypothalamus and septum + nucleus аccumbens of rats with alcohol dependence. Materials and methods. The studies were carried out on 50 nonlinear white adult male rats in a chronic experiment in 3 groups: intact rats; rats with alcohol dependence; rats with alcohol dependence and intranasal SNP administration. The model of alcohol dependence was created by voluntary alcohol intake at a dose of 1.25 g/kg body weight of rat for 35 days. SNP was administered intranasal at a dose of 8 μg/kg body weight of the animal. The level of anxiety was determined by means of neuroethological tests: multi-parameter comprehensive assessment of anxiety, «open field» and «tail suspension test». The electrical activity of LNCSB was registered by the stereotactic introduction of electrodes. The concentration of NO was investigated in the hippocampus, hypothalamus, septum + nucleus аccumbens Results. Intranasal administration of SNP to rats with alcohol dependence led to suppression of convulsive and paroxysmal activity, caused by alcoholization and withdrawal of alcohol, on the electroencephalogram of the structures of the LNCSB and increased the absolute power of biopotentials of the delta and theta ranges on the spectrogram of the hippocampus. Reduction of anxiety was found in rats with a high baseline level of anxiety accompanied by recovery of NO level, which was depleted by chronic alcoholization, in the hypothalamus and hippocampus. Conclusions. Intranasal administration of SNP as a NO donor causes anxiolytic effects in the state of alcohol withdrawal depending on the baseline level of anxiety: in rats with the high baseline level of anxiety – reduces this level; in rats with the low baseline level – restrains it at the level of anxiety after alcohol intake. Intranasal administration of SNP to the rats with alcohol withdrawal causes positive changes in the electroencephalogram of the LNCSB, which are manifested in suppression of convulsive and paroxysmal activity and enhancement of brain biopotentials in alpha and delta ranges on spectrogram of hippocampus with sustaining this effect for whole day. Intranasal administration of SNP is a source of short-term supply of NO to brain cells, which leads to the restoration of NO levels in the hypothalamus, hippocampus, septum and nucleus accumbens – structures that are involved in the regulation of emotional motivational behavior. Key words. limbic-neocortical system of the brain, model of alcohol dependence, anxiety, nitric oxide, sodium nitroprusside