Alcohol-induced poikilothermia, sleep and motor impairment: actions on brain of EGTA and verapamil.
In the early 1970's, calcium ions were implicated in the mechanism underlying the perturbation of the "set point" for body temperature produced by a thermolytic drug. Since Ca++ is thought to be involved in the incapacitating effects of ethanol on body temperature and motor coordination, this investigation sought to compare the differential central actions of a Ca++ chelating agent with those of a Ca++ channel antagonist on ethanol-induced poikilothermia and motor functions. A chronically indwelling cannula for intracerebroventricular (ICV) injection was implanted stereotaxically in each of 25 adult male Sprague-Dawley rats. Following postoperative recovery, each rat was given ethanol in a 20% v/v solution by the intraperitoneal route in a dose of 4.0 g/kg, which was selected to insure a clear-cut impairment of autonomic and motorial functions. Colonic temperature, behavioral sleep, righting reflex and degree of motor coordination on a rotorod were monitored at selected intervals for 5.0-7.0 hr after the injection of ethanol. Two experimental designs were used: First, either 12.5, 25 or 50 micrograms ethyleneglycol-bis-(beta-amino ethyl ether) N,N'-tetra-acetic acid (EGTA), or 25 or 50 micrograms verapamil, both dissolved in an artificial CSF vehicle, were infused ICV at the same time as ethanol's administration. In the second design, the compounds were infused at the nadir of the ethanol-induced temperature decline. EGTA infused ICV in the rat together with ethanol produced a dose-dependent inhibition of ethanol hypothermia and a more rapid recovery of the animal's righting reflex, arousal and motor coordination than that following ethanol alone. Although verapamil infused ICV in the 50 micrograms but not 25 micrograms dose minimized the poikilothermic response to ethanol, it was not as efficacious as that of EGTA. When infused ICV at the point of maximum fall in the rats' temperature. EGTA entirely reversed the hypothermia induced by ethanol and evoked a thermogenic response in the rat. In contrast, verapamil infused ICV in the same doses tended only to retard the further decline in the animal's body temperature. Similarly EGTA was far more effective than verapamil in ameliorating the other physiological actions of ethanol in terms of the reversal of areflexia, behavioral sleep and motor incoordination. These results suggest that the characteristic attributes of membrane Ca++ in terms of its binding and other neuronal properties play a significant functional role in the incapacitating action of ethanol on the diverse physiological processes mediated by the brain.(ABSTRACT TRUNCATED AT 400 WORDS)
Paez
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Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27834.
Myers
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D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004533:Egtazic Acid / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000139:chemically induced*; D014700:Verapamil / Q000494:pharmacology*
D000431:Ethanol; D004533:Egtazic Acid; D014700:Verapamil