The effects of GABA agonists and antagonists on apomorphine-induced climbing behavior

Abstract

Apomorphine administered at a dose of 1.5 mg/kg SC induces an intense climbing behavior in mice lasting for approximately 30 min. It is known that neuroleptics attenuate apomorphine climbing behavior (AC) but the influence of GABA agonists and antagonists on this behavior is unclear. The GABA agonist, muscimol, blocked AC with an ED 50=0.9 mg/kg IP. Pretreatment (5 hr) with aminooxyacetic acid (50 mg/kg IP), a GABA-T inhibitor, produced a 65% inhibition of AC. The GABA antagonists, picrotoxin and bicuculline, had little effect on AC. Baclofen had no effect on AC from 0.5 to 4 mg/kg IP. Interaction studies, combining muscimol and haloperidol were conducted to evaluate the interaction between GABA-ergic and dopaminergic systems on AC. In the first studies mice were treated with haloperidol (0.04-0.15 mg/kg SC) then challenged with inactive (0.2 mg/kg IP) and active (0.4 mg/kg IP) doses of muscimol. In the second series of studies mice were treated with muscimol (0.25-1 mg/kg IP) then challenged with inactive (0.04 mg/kg SC) and active (0.08 mg/kg SC) doses of haloperidol. In all of these experiments, there was an enhanced suppression of AC. Our studies suggest that in addition to dopamine antagonists, GABA agonists are also capable of blocking AC. Our results further suggest that the effect of GABA agonists in inhibiting AC may be mediated through dopaminergic neurons.