Alcohol, acetaldehyde and salsolinol-induced alterations in functions of cerebral GABA/benzodiazepine receptor complex.
Effects of alcohol (ethanol) and acetaldehyde on the metabolism and function of primary cultured GABAergic neurons and that of salsolinol, a condensation product of acetaldehyde with dopamine, on cerebral GABA/benzodiazepine (BZP) receptor complex were investigated. In vitro addition of acetaldehyde induced a significant reduction not only on the content of GABA but also on the basal and GABA-activated [3H]flunitrazepam ([3H]FLN) bindings in primary cultured neurons. In contrast, alcohol exhibited only suppressive effects on [3H]FLN binding as well as on the enhancement of [3H]FLN binding by GABA. On the other hand, salsolinol showed a significant stimulatory effect on [3H]FLN binding to cerebral particulate fractions obtained from alcohol-untreated mice in the presence of NaCl. Although a similar activation of cerebral [3H]FLN binding by salsolinol was found in alcohol-treated mice, this activation was significantly weaker in alcohol-withdrawn mice than those found in alcohol-untreated as well as alcohol-inhaled mice. These results strongly suggest that acetaldehyde may have more important pathophysiological roles than those of alcohol in the exhibition of neurotoxicity during alcohol intake. The present results also suggest that salsolinol may have a modulatory role on cerebral benzodiazepine receptor and the decreased capacity of such a modulating mechanism may be involved in the exhibition of alcohol withdrawal syndrome, possibly by decreasing the function of endogenous ligands for benzodiazepine receptor in the brain.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000079:Acetaldehyde / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005971:Glutamates; D007546:Isoquinolines; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D018698:Glutamic Acid; D005445:Flunitrazepam; C046308:tert-butylbicyclo-2-benzoate; C036617:salsolinol; D002795:Choline O-Acetyltransferase; D000612:4-Aminobutyrate Transaminase; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; D000079:Acetaldehyde