Chronic Effect of Ethanol Ingestion on Flunitrazepam Binding to GABA Receptors of Rat Brain Synaptosoms Effect of ethanol on GABA receptors
Journal Title:Journal of Neurology, Psychiatry and Brain Research
Purpose: Changes in the CNS functions associated with ethanol ingestion are suggested to be related to the involvement of several neurotransmitter receptor systems, including the GABA receptor complex. The aim of this study is to investigate the effects of chronic exposure of ethanol ingestion on gamma-aminobutyric acid (GABA) - benzodiazepine receptor complex in four rat brain regions.
Materials and Methods: Male Wistarrats were housed with food and drinking water/ethanol (85%+15% v/v). After 13 months of chronic ethanol consumption, the rats were killed by decapitation and the brain regions dissected and the synaptosome fractions prepared on Ficoll-sucrose gradient centrifugation procedure(4°C). The resulting pellet was resuspended in 1 ml of Tris-Hclbuffer (pH 7.4) and binding assay carried out in the presence of [3H] Flunitrazepam.
Results: Chronic ethanol ingestion by the rat resulted in an increase of receptor affinity in the striatum and hippocampus, and a decrease in the receptor affinity in the cerebellum and frontal cortex. GABA receptor density, as assessed by GABA-benzodiazepine binding (B max), was decreased insignificantly in the all brain regions studied. The different responses of GABA receptor affinity of the brain regions to chronic ethanol ingestion may result from quantitative differences in the distribution of GABA-ergic neurons in the tested brain areas.
Conclusions: The increase in the affinity of the striatum and hippocampus and the decreased affinity of the cerebellum and frontal cortex suggested that up-regulation of these receptors may be Induced by chronic ethanol ingestion.