Mechanisms of alcohol intoxication in a rodent model: blunted alcohol-opposing reaction in "alcohol-sensitive" rats.
In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena.
Korpi
E R
ER
Research Laboratories, Alko Ltd, Helsinki, Finland.
Tuominen
K
K
Uusi-Oukari
M
M
Saransaari
P
P
Oja
S S
SS
Suzdak
P D
PD
D000311:Adrenal Glands / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000493:pharmacokinetics; D003348:Cortisone / Q000097:blood; D004195:Disease Models, Animal; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006185:Habituation, Psychophysiologic; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D013331:Strychnine / Q000493:pharmacokinetics
D001570:Benzodiazepinones; D003292:Convulsants; C028513:4'-chlorodiazepam; D000431:Ethanol; D013331:Strychnine; D003348:Cortisone