GABAergic actions of THIP in vivo and vitro: a comparison with muscimol and GABA.

GABAmimetic actions of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were evaluated both in vivo and in vitro and compared with the actions of muscimol and GABA. The GABAergic potencies of these agents were assessed in vivo by measuring their ability to inhibit firing of rat substantia nigra pars reticulata neurons after systemic administration and iontophoretic applications, and in vitro by measuring their ability to inhibit 3H-GABA binding to rat cerebellar membranes. The effects of THIP were found to be similar to those of muscimol and GABA with regard to inhibition of reticulata cell firing and 3H-GABA binding. The order of potency was muscimol > GABA > THIP. The magnitude of the differences between drug potencies in iontophoretic studies closely paralleled their relative potencies in binding studies, with muscimol approximately 3 times more potent than GABA and 25-40 times more potent than THIP. After systemic (i.v.) administration, however, muscimol was only 3 times more potent than THIP in inhibiting reticulata cell firing, possibly because THIP passes the blood-brain barrier more readily.