The relationship between baseline prepulse inhibition levels and ethanol withdrawal severity in rats

Baseline prepulse inhibition (PPI) of the acoustic startle reflex is thought to reflect the functioning of the sensorimotor gating system in the brain. The current literature indicates that similar neurotransmitter systems may play roles both in the regulation of PPI and in the development of ethanol withdrawal syndrome (EWS). The aim of the present study was to test if individual baseline PPI levels have any relationship to the behavioral and neurochemical consequences of EWS in rats. A batch of rats (n = 30) was sorted according to baseline PPI levels and classified as either high-inhibitory (HI) or low-inhibitory (LI) rats (n = 10 in each group). Ethanol was administered in a liquid diet for 21 days. On the 22nd day, ethanol was removed from the diet, and EWS was induced. At the 2nd, 4th, and 6th hours of EWS, locomotor activity and behavioral symptoms were evaluated. Brain tissue concentrations of dopamine, serotonin and noradrenaline in hippocampus, cortex, and striatum were measured after the 6th hour of EWS testing. Another batch of rats (n = 30) was classified using the same procedure and fed with regular diet. On the 22nd day, rats were decapitated and neurochemical measurements were repeated. HI and LI rats consumed similar amounts of ethanol. However, EWS signs such as stereotyped behaviors, wet-dog shakes, and tremor were more intense in LI rats compared to their HI counterparts. Audiogenic seizures occurred in both groups in a similar manner. Although the catecholamine concentrations in the brains of both groups were parallel under baseline conditions, dopamine levels increased in the cortex of LI and in the striatum of HI rats, whereas striatum serotonin levels decreased only in LI rats after the 6th hour of EWS. In conclusion, the data suggest that the behavioral symptoms and neurochemical changes observed in EWS may be associated with baseline PPI levels.

Research Highlights
► Ethanol withdrawal is more severe in the rats with low baseline PPI.
► Ethanol withdrawal increased cortical dopamine only in low-inhibitory rats.
► Ethanol withdrawal increased striatal dopamine only in high-inhibitory rats.
► High alcoholism prevalence in psychotic patients is linked to low sensorimotor gating.