SL76002 - effect on gamma-aminobutyric acid and dopamine in animals treated chronically with haloperidol

Daily haloperidol injection at the dose of 5 mg/kg for 34 days did not change the levels of dopamine in the corpus striatum, frontal cortex, and midbrain of rats. However, the gamma-aminobutyric acid (GABA) level was increased by 27% in the corpus striatum. Haloperidol withdrawal for 4 days after 30-day treatment increased GABA levels of the corpus striatum and the frontal cortex to 140 and 125%, respectively, of control values. GABA, by its inhibitory actions, depleted dopamine level in the corpus striatum and frontal cortex by 17 and 29%, respectively. Administration of SL76002, a new GABA agonist, for 4 days at the dose of 400 mg/kg i.p. to haloperidol-withdrawn rats increased GABA levels in striatum by 23% of control values. The dopamine levels were also decreased significantly in the frontal cortex and corpus striatum. Our data demonstrate that SL76002, by altering the GABA levels, probably influences DA functioning in the corpus striatum, a region responsible for involuntary movements.