The role of GABA-b receptor activity in central purinergic system in mice

A behavioral study was performed in an attempt to clarify an interaction between the GABA-b and the adenosine A_1 receptors in aggressive behaviors induced by clonidine in mice. Mice administered high doses of clonidine (20-30mg/kg i.p.) exhibited aggressive behaviors such as biting and attacking. Baclofen (1-5mg/kg), a GABA-b receptor agonist, inhabited the aggressive behaviors induced by clonidine (20mg/kg) in dose-dependent manner. Caffeine (5-10mg/kg), an adenosine (A_1＞A_2) receptor antagonist, markedly potentiated the aggressive behaviors. The inhibitory effect og baclofen (1mg/kg) on the aggressive behaviors induced by clonidine (20mg/kg) was antagonized by caffeine (5mg/kg). Furthermore the stimulatory effedt of caffeine (5mg/kg) was reversed by baclofen. Aminooxyacetic acid (AOAA : 30mg/kg), a GABA transaminase inhabitor, also reduced clonidine (30ng/kg) induced aggressive behaviors. The inhibitory effect of AOAA tended to be increaced by bicuculline (2mg/kg), a GABA-a receptor antagonist, but did not significantly. The inhibitory effect of combined treatment with AOAA and bicuculline on the aggressive behaviors was antagonized by caffeine (1mg/kg), whereas the stimulatory effect of caffeine on the behaviors was reversed by combined treatment with these drugs. The results suggest that since either baclofen (GABA-b receptor agonist) or AOAA (endogenous GABA) in hibits colonidine-induced aggressive behaviors which are potentiated by caffeine, an adenosine receptor antagonist, these agents may be, in part, similar to the mode of action of adenosine receptor agonist.