Changes in cognitive behavior in alcohol-dependent rats under conditions of brain nitric oxide synthase blockade

Abstract

Alcohol use disorder (AUD) is accompanied by dysfunction in neural networks that control motivation, emotion, cognition, and behavioural flexibility. The hypothalamus, as a key regulator of physiology and neuroendocrine activity, influences eating behaviour and executive functions. Behavioural inflexibility in AUD can be both a consequence and a marker of the addictive process. The aim of the study was to evaluate the relationship between working memory and executive functions during food-seeking activity in rats with a model of alcohol dependence under pharmacological blockade of the nitric oxide synthase (NOS) enzyme system. The study used four groups of male rats (n=8) that underwent food deprivation and conditional task training. AUD was modelled by administering 20% ethanol for 30 days. After administration of the selective nitric oxide synthase inhibitor 7-nitroindazole, cognitive behaviour, motor activity, urination and spatial alternation in the Y-maze were assessed. Alcohol impaired the formation of feeding habits and caused stress reactions. Inhibition of nitric oxide synthase (NOS) reduced polyuria and partially restored cognitive flexibility. The data obtained indicate the important role of the hypothalamic nitric oxide system in regulating behaviour in AUD and its potential as a therapeutic target.