Brain regional gamma-aminobutyric acid (GABA) and locomotor activity: effect of long-term aldrin exposure.

Aldrin-induced stimulation of locomotor activity (LA) under nontolerant conditions was restored to control value after 20 or more consecutive days of aldrin administration. In contrast to the inhibition of GABAergic activity with aldrin under short-term conditions as observed in our previous study, the measurement of steady-state level of GABA, the activities of its metabolizing enzymes, turnover and the specific binding of GABA to its receptor in different regions of the brain of rats treated with aldrin (2 or 5 mg/kg/day, po) under long-term (for 30 consecutive days) conditions showed no change in the GABAergic activity in any regions of the rat brain. Moreover, the studies of the interaction between neurotransmitters (using agonist(s) and antagonist(s) of the respective neurotransmitter receptors) showed that long-term administration of aldrin restored the LA to control value by upregulation of central GABAergic activity through the interaction with dopaminergic and cholinergic systems. Thus, this result suggests that long-term aldrin exposure upregulated the central GABAergic activity inhibition under short-term aldrin treatment which may be a cause of restoration of LA stimulated by the short-term aldrin administration to its control value.