Interaction of dopamine, nitric oxide and testosterone in the brain system of motivational reinforcement in rats with alcohol dependence and under nitric oxide donator impact

Abstract

The complex of neurophysiological methods (stereotaxic implantation of electrodes into brain structures, recording of electrical activity of the neocortex, hippocampus, hypothalamus, and nucleus accumbens) was applied to 65 laboratory male rats with models of chronic alcoholization (during 40 days of alcohol consumption in dose 1.25 g/kg body mass) and alcohol withdrawal during 2 days. The leading role of functional changes of electrogenesis in hippocampus, hypothalamus and nucleus accumbens has been revealed in rats being in states of alcohol dependence. The highest absolute spectral powers of oscillations of the β and Ѳ rhythms in the hippocampus and manifestations of generalized hypersynchronous activity with initiation in the hippocampus and hypothalamus were noted in rats under alcohol dependence. The paroxysmal pattern of activity on EEG of the structures of the limbico-neocortical system acquired an “explosive” character after alcohol withdrawal. The complex of neurochemical methods (detection of dopamine and testosterone concentration with enzymoimmunoassay and nitric oxide concentration with spectrophotometric analysis in the brain structures and serum) was carried out after 40 days of alcoholization as well as after 2 days of alcohol withdrawal. Decreased levels of testosterone and nitric oxide were identified in hypothalamus and hippocampus as well as testosterone in nucleus accumbens and serum. There were observed increased dopamine release in nucleus accumbens in response to latest dose of alcohol consumption and recovery of dopamine level after alcohol withdrawal. To the contrary, the dopamine content decreased in hypothalamus in the state of alcohol withdrawal. The five-time (twice a day) intranasal introduction of sodium nitroprusside repaired nitric oxide and testosterone levels in the brain structures of motivational reinforcement and suppressed seizure pattern on EEG but didn’t change testosterone concentration in serum. Obtained data are considered as one of the important aspects of interactions in the system of hormonal-neurotransmitter-metabolic regulatory mechanisms of motivational reinforcement under formation and suppression of alcohol dependence.