Environmentally-induced modification of the benzodiazepine/GABA receptor coupled chloride ionophore

R. Trullas, H. Havoundjian, N. Zamir, S. Paul, P. Skolnick

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73 Scopus citations

Abstract

The benzodiazepine/GABA receptor coupled chloride ionophore was examined in brain membranes of rats maintained in either a conventional animal facility or a "protected" (low-stress) environment. Following a 10 min ambient temperature swim, animals maintained in both environments had qualitatively similar increases in the number (Bmax) of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, the apparent affinity of this radioligand, and the efficacy and potency of Cl- to enhance [3H]flunitrazepam binding. Nonetheless, the Bmax of [35S]TBPS and efficacy of Cl- to enhance [3H]flunitrazepam binding were significantly lower in animals housed in the protected environment compared to those maintained in a conventional facility both before and after swim stress. Furthermore, in rats housed in a protected environment, sequential removal of animals from a common cage (cohort removal), produced a very rapid increase (≤15 s) in Cl--enhanced [3H]flunitrazepam binding in cortical and hippocampal but not cerebellar membranes. Cohort removal also produced a sequential increase in the number of [35S]TBPS binding sites and apparent affinity of this radioligand in cerebral cortical membranes. The effects of cohort removal were not observed in animals subjected to ambient temperature swim or if animals were removed from different cages. Changes in the benzodiazepine/GABA receptor coupled chloride ionophore produced by cohort removal from a common cage preceded any statistically significant changes in circulating levels of α-MSH, β-endorphin, ACTH or corticosterone. These findings suggest that the benzodiazepine/GABA receptor chloride ionophore complex (supramolecular complex) is under both tonic and acute regulation by the environment, and may subserve a physiologically relevant function in the response to stressful or anxiety producing stimuli.

Original languageEnglish
Pages (from-to)384-390
Number of pages7
JournalPsychopharmacology
Volume91
Issue number3
DOIs
StatePublished - Sep 1 1987

Keywords

  • Benzodiazepine receptors
  • Chloride ionophore
  • Housing
  • Stress
  • t-Butylbicyclophosphorothionate

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