Increased alcohol intake and behavioral disinhibition in rats with ventral striatal neuron loss.

A previous study of ours reported excessive alcohol intake, enhanced defensive aggressiveness (hyperreactivity towards the experimenter), impulsive behavior, and reduced cortical serotonin levels in rats following extensive basal forebrain axon-sparing lesions involving the septal area and the ventral striatum. This constellation of signs resembles that seen clinically in "Dionysian" alcoholics. The present investigation aimed at examining the effect of ibotenic acid lesions restricted to the septal area or the ventral striatum on this behavioral profile. Experiment 1 indicated that medium-sized lesions (induced by infusing 0.35 microl ibotenic acid in each hemisphere) encompassing the septal area or the ventral striatum elicited a qualitatively similar behavioral profile. Both lesion types markedly enhanced the intake of 6% ethanol, and both groups were significantly more hyperreactive towards the experimenter. A brief doorbell signal elicited significantly more fleeing in rats with basal forebrain lesions, and licking from an electrified waterspout in the punished drinking test caused lesser suppression of locomotor activity than normal. Both groups also showed significant deficits in food hoarding. Histological examination revealed that the posterior portion of the ventral striatal lesion typically overlapped with the anterior portion of the septal lesion. Experiment 2 avoided this neuropathological overlap, and examined groups bearing small discrete lesions (induced by infusing 0.15 microl ibotenic acid in each hemisphere) restricted to either the accumbens part of the ventral striatum or the dorsal septal area. Lesions to the nucleus accumbens were associated with an increase in home-cage alcohol drinking, no hyperreactivity towards the experimenter, potentiation of fleeing at the expense of freezing in response to a sudden auditory signal, and disinhibited behavior in the punished drinking test with increased punished responding and reduced behavioral suppression. Rats with small septal lesions showed a weak enhancement of defensive aggression, but no other behavioral alterations. Our results suggest that ventral striatal neuron loss gives rise to excessive alcohol drinking and enhanced impulsivity.