Caffeine-induced locomotor activity: possible involvement of GABAergic-dopaminergic-adenosinergic interaction

Caffeine (10-40 mg/kg, p.o.) enhanced locomotor activity (LA). Administration of GABA antagonist, bicuculline (0.5-1.0 mg/kg, i.p.), potentiated this caffeine-induced increase of LA, as well as LA of control rats. Treatment with the GABA agonist, muscimol (0.25-1 mg/kg, i.p.) or dopaminergic antagonist, haloperidol (0.25-1 mg/kg, i.p.) or muscarinic receptor blocker, atropine (3.75-5 mg/kg, i.p.), or inhibitor of acetylcholine esterase physostigmine (0.05-0.30 mg/kg, i.p.) or nicotine (0.5-1.5 mg/kg, i.p.) an nicotinic receptor agonist all decreased the LA of both caffeine-treated and control rats. Haloperidol-induced reduction in caffeine-induced increase in LA was found to be withdrawn with higher dose of caffeine. The dopamine agonist L-Dopa (75-150 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) increased the LA in control rats and potentiated the LA of caffeine treated rats. The haloperidol attenuated the bicuculline-induced increase in LA and atropine or physostigmine attenuated the bicuculline or L-Dopa + carbidopa-induced increase in LA in both caffeine treated and control rats when those drugs were administered concomitantly with bicuculline or L-Dopa+carbidopa. These results suggest that (a) the GABAergic system has direct role in the regulation of LA, and (b) caffeine potentiates LA by antagonism of the adenosine receptor and activation of the dopaminergic system which, in turn, reduces GABAergic activity through the reduction of cholinergic system.