INHIBITION OF GABA TRANSAMINASE ENHANCES LIGHT-INDUCED CIRCADIAN PHASE DELAYS BUT NOT ADVANCES

The CNS neurotransmitter GABA is distributed extensively throughout th e suprachiasmatic nucleus, the site of circadian pacemaker cells in ma mmals. Pharmacological agents that act at GABAA receptors alter specif ic circadian responses to light and may induce phase shifts of circadi an rhythms. In the present study, the role of endogenously released GA BA in rhythm regulation was investigated using vigabatrin (gamma-vinyl GABA), an agent that has been shown to increase chronically or acutel y the CNS levels of this neurotransmitter by inhibiting GABA transamin ase. In Experiment 1, hamsters in constant darkness (DD) received a sa line or a vigabatrin injection 1 hr before a 15-min, 700-lux light pul se. Vigabatrin increased photic phase delays but did not affect advanc es. In Experiment 2, vigabatrin delivered chronically via osmotic mini pump treatment did not affect locomotor activity period in DD. However , after 14 days of infusion, photic phase delays (but not advances) we re greatly increased in the vigabatrin group. In Experiment 3, in cons tant light (LL), chronic vigabatrin-treated animals showed an increase d period that returned to pretreatment values after the 14-day drug in fusion. The results are consistent with the phase-dependent effects of other agents that alter GABA neurotransmission. The data support the general hypothesis that GABA modulates the circadian responses to ligh t in a phase-dependent manner, and may participate in entrainment to l ight-dark cycles by influencing the relative responsiveness to light i n the early and late subjective night.