GABA(A) RECEPTOR-BINDING IN THE AGING RAT INFERIOR COLLICULUS

The inhibitory neurotransmitter GABA has been shown to be critically i nvolved in shaping neuronal responses to simple and complex acoustic s timuli in the inferior colliculus. Studies in the rat and human inferi or colliculus have suggested significant changes in functions related to GABA neurotransmission occur in the aged. These changes include sig nificant decreases in GABA content, GABA release, GABA neurons, glutam ate decarboxylase enzymatic activity, and GABA(B) receptor binding. Su ch changes within the inferior colliculus may affect the ability of el derly listeners to process complex acoustic signals, particularly in t he presence of background noise. The present study was designed to exa mine the regional distribution and effects of aging on GABA(A) recepto r binding sites in the Fischer 344 rat inferior colliculus using in vi tro quantitative receptor autoradiography. [H-3]GABA binding to GABA(A ) receptors was significantly reduced in the inferior colliculus of yo ung adult (3 months) and aged (18-26 months) rats when compared to 2-m onth animals. However, no significant changes were observed after 3 mo nths of age. Single concentrations of tritiated GABA(A) receptor ligan ds (muscimol, t-bulylbicycloorthobenzoate, and flunitrazepam) revealed no significant age-related changes in receptor binding in the inferio r colliculus between 3 and 26 months of age. To characterize further t he pharmacology of the GABA(A) receptor in the inferior colliculus, GA BA modulation of the picrotoxin binding site was examined using [H-3]t -butylbicycloorthobmzoate. When increasing concentrations of GABA were added to the incubation buffer, a significant decrease in binding was observed in the inferior colliculus of rats in each age group. In age d rats, the dose-response curve was shifted to the left, indicating an increase in the potency of GABA to inhibit [H-3]t-butylbicycloorthobe nzoate binding. Although no changes in GABA(A) receptor binding were d etected in the inferior colliculus after 3 months of age, a significan t alteration in interaction between the GABA and picrotoxin binding si tes was observed in the inferior colliculus of aged rats when compared to 3-month-old young adults. This difference appears to reflect an in creased sensitivity of the receptor to GABA modulation in aged rats an d, thus, may serve as a compensatory mechanism to enhance GABA(A) rece ptor function in response to a presynaptic loss of inhibition. Copyrig ht (C) 1996 IBRO. Published by Elsevier Science Ltd.