Inhibition of GABA transaminase enhances light-induced circadian phase delays but not advances.
The CNS neurotransmitter GABA is distributed extensively throughout the suprachiasmatic nucleus, the site of circadian pacemaker cells in mammals. Pharmacological agents that act at GABAA receptors alter specific circadian responses to light and may induce phase shifts of circadian rhythms. In the present study, the role of endogenously released GABA in rhythm regulation was investigated using vigabatrin (gamma-vinyl GABA), an agent that has been shown to increase chronically or acutely the CNS levels of this neurotransmitter by inhibiting GABA transaminase. In Experiment 1, hamsters in constant darkness (DD) received a saline or a vigabatrin injection 1 hr before a 15-min, 700-lux light pulse. Vigabatrin increased photic phase delays but did not affect advances. In Experiment 2, vigabatrin delivered chronically via osmotic minipump treatment did not affect locomotor activity period in DD. However, after 14 days of infusion, photic phase delays (but not advances) were greatly increased in the vigabatrin group. In Experiment 3, in constant light (LL), chronic vigabatrin-treated animals showed an increased period that returned to pretreatment values after the 14-day drug infusion. 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 light in a phase-dependent manner, and may participate in entrainment to light-dark cycles by influencing the relative responsiveness to light in the early and late subjective night.
Golombek
D A
DA
Department of Psychology, University of Toronto, Ontario, Canada.
Ralph
M R
MR
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D008027:Light; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects; D017440:Photoperiod; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin