SENSITIVITY TO ETHANOL ACROSS DEVELOPMENT IN RATS - COMPARISON TO [H-3]ZOLPIDEM BINDING

Previous research has suggested that rats tested at 28 to 30 days of a ge show a marked subsensitivity to the sedative effects of ethanol. In the present study, rats of different ages were tested for aerial righ ting following acute ethanol (3 g/kg) treatment. These results were co mpared with the effects of the atypical benzodiazepine zolpidem (3 and 5 mg/kg) and pentobarbital (10 and 15 mg/kg). Animals tested at 25, 2 8, or 35 days of age were significantly less impaired by ethanol than preweanling rats (age 20 days) or older rats (age 65 to 75 days), wher eas animals tested at 25 or 28 days of age were less impaired by the h igher dose of zolpidem. With pentobarbital, the most distinct age-rela ted trend was greater impairment in 20-day-old rats. Because ethanol m ay be active at the same type I GABA(A) receptor site selectively labe led by [H-3]zolpidem, levels of [H-3]zolpidem binding were determined for rats of different ages. Although some brain regions showed progres sive increases in binding of [H-3]zolpidem across development, other r egions demonstrated increased binding from day 12 or 17 to day 20, the n a plateau of binding levels across days 20, 25, and 28, with further increases occurring by day 36 or day 60. This pattern was observed in the cingulate cortex, medial septal nucleus, globus pallidus, inferio r colliculus, red nucleus, and cerebellum. Overall, the results indica te that the period of subsensitivity to the sedative effects of ethano l is coincident with a change in the developmental pattern of GABA(A) receptor sites targeted by [H-3]zolpidem.