Effect of baclofen and haloperidol on γ-aminobutyric acid and dopamine systems in an animal model of tardive dyskinesia

Abstract 1. The effects of 5 days treatment with baclofen (20 mg/kg, i.p.) or high doses of haloperidol (10 mg/kg, i.p.) were studied on dopamine and γ-aminobutyric acid levels of corpus striatum, frontal cortex and mid-brain of normal rats as well as those withdrawn for 4 days after 30 days of daily treatment with haloperidol (1 mg/kg). 2. Baclofen treatment slightly but significantly increased (by 13%) GABA levels in the corpus striatum of normal rats. This, by inhibitory effects, probably depleted dopamine level in corpus striatum. 3. In the mid-brain, no change in GABA level was observed after baclofen treatment. The frontal cortex, which receives dopaminergic nerve endings from cell bodies lying in the ventral tegmental area, showed high levels of dopamine. 4. Administration of baclofen to haloperidol-withdrawn rats tended to further increase GABA levels in striatum; however, the change was not statistically significant. In contrast, mid-brain GABA levels were decreased by 21% when compared with haloperidol-withdrawn values taken as 100%. 5. Baclofen treatment increased DA level by 66% in the frontal cortex and decreased it by 35% in striatum of rats. 6. In normal rats, administration of high doses of haloperidol (10 mg/kg) increased GABA levels of the corpus striatum and the frontal cortex by 48 and 16%, respectively. 7. In mid-brain, a slight increase (11%) was reported in GABA level. 8. Haloperidol treatment decreased DA in striatum, but increased it in the mid-brain and the frontal cortex. High doses of haloperidol for 5 days to rats previously treated with haloperidol (1 mg/kg) daily for 30 days and subsequently withdrawn for 4 days produced no further change in GABA levels of various brain areas examined. In mid-brain, a slight decrease was seen in GABA level. 9. Haloperidol treatment in high doses of haloperidol-withdrawn rats decreased DA level in corpus striatum by 43%, but increased it in the frontal cortex and mid-brain as was seen in normal animals. 10. Our data demonstrated that high doses of haloperidol, like baclofen, enhanced the functioning of GABAergic neurons in striatum, which in turn, influenced the DAergic system in this brain area.