Intranigral GABAergic drug effects on striatal dopamine activity

Concentrations of striatal dopamine (DA), serotonin (5-HT) and their metabolites were measured following infusions ofthe GABA_A receptor agonist, muscimol, or GABA_A receptor antagonist, bicuculline, into the substantia nigra (SN) or areas dorsal to the SN in adult rats and 16-day-old rat pups. Results indicated that intranigral infusions of muscimol produced site-specific increases in the concentrations of striatal DA metabolites in adults, while in pups, intranigral muscimol infusions produced site-specific increases in the concentrations of striatal DA. Intranigral infusions of bicuculline had no effect on striatal DA or its metabolites in either age group. Neither GABAergic drug had any effect on striatal 5-HT or its metabolite. The data suggest that the effect of nigral GABA_A agonist infusions on the activity of the nigrostriatal pathway is age-specific. The lack of opposing effects following the nigral infusion of a GABA_A receptor antagonist indicates that the influences of GABA_A agonist may be mediated by different mechanisms as a function of age.