Experience influences environmental modulation of function at the benzodiazepine (BZD)/GABA receptor chloride channel complex

Abstract

Function of the benzodiazepine (BZD)/GABA receptor chloride channel complex was selectively altered by specific aspects of an environmental challenge, i.e. encountering a stranger in a familiar versus an unfamiliar environment. Chloride (Cl-) enhancement of [3H]flunitrazepam [( 3H]flu) binding was facilitated in rats tested in an unfamiliar environment relative to that in rats tested in a familiar environment. Basal [3H]flu binding (binding in the absence of NaCl) also was greater in rats tested in the unfamiliar environment than in rats tested in the familiar environment, and Scatchard analysis of [3H]flu binding indicated that increased [3H]flu binding in the unfamiliar environment reflected an increase in both binding affinity and maximal binding capacity. In addition, both the sensitivity of [3H]flu binding to Cl- and the affinity of BZD recognition sites were decreased in handled control rats relative to non-handled control rats as well as to environmentally-challenged (prehandled) rats, suggesting that the experience of daily handling as well as familiarization with the environment modulates function at the BZD/GABA receptor complex. GABA-mediated 36Cl- uptake was facilitated by testing in either the familiar or unfamiliar environment relative to that measured in non-handled control rats. Thus, changes in GABA-gated chloride channel function may reflect a more fundamental response of this complex to challenging situations. These findings suggest that components of the BZD/GABA receptor complex are differentially influenced by specific aspects of an environmental challenge. Furthermore, function at the BZD recognition site/chloride channel component of this receptor complex is influenced by both repeated and single exposure to specific environments.