Chronic infusion of GABA into the nucleus basalis magnocellularis or frontal cortex of rats: a behavioral and histological study.

In order to determine the influence of the nucleus basalis magnocellularis (NBM) on the sensorimotor function of the frontal cortex (FCx) of the rat, GABA at various concentrations (10, 50 or 100 micrograms.microliters-1) was administered into these structures. GABA was infused for four consecutive days after which saline was infused for another four. On the contralateral side the order of administration was reversed. Each structure received GABA while its homologous on the contralateral side received saline. Before, during and after drug infusion, the animals were weighted and their performance in two non-reinforced behavioral tasks (beam walking and spontaneous rotation) was examined. When GABA was infused into the FCx, a dose-dependent and reversible sensorimotor deficit was observed along with a behavioral withdrawal syndrome upon GABA discontinuation. When GABA was administered into the NBM, a reversible sensorimotor deficit was observed only when GABA was infused at the highest concentration. In this case no behavioral changes were observed upon GABA discontinuation. Histologically, a gliosis was observed in the NBM in which GABA was infused at the two highest concentrations without saline pretreatment; these effects were not observed when GABA was infused without saline pretreatment into the FCx. In relation to our previous findings, these results suggest that i) the FCx is directly involved in the expression of sensorimotor functions, while the influence of the NBM on these functions appears only after severe subcortical damage, ii) a GABA withdrawal syndrome is observed following GABA administration in the FCx but not in the NBM, and iii) "tonic" effects of GABA are dose-related and partially dependent upon pretreatment conditions and the brain region infused.