Brezenoff_1976_Eur.J.Pharmacol_37_125

Reference

Title : Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3 - Brezenoff_1976_Eur.J.Pharmacol_37_125
Author(s) : Brezenoff HE , Mycek MJ
Ref : European Journal of Pharmacology , 37 :125 , 1976
Abstract :

Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, respectively. A 40-60% reduction in this response was obtained following administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed function oxidase activity, this enzyme induction was shown to be unrelated to the development of tolerance to loss of righting reflex. I.c.v. injection of hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 mug) profoundly affected tolerance to the central depressant effect of the barbiturates. Thus, depending upon the time of administration, HC-3 either retarded or prevented development of this tolerance. Moreover, if tolerance was allowed to progress normally, administration of HC-3 on day 4 or 5 returned the duration of the loss of righting reflex toward normal values. HC-3 did not influence either the duration of this response in non-tolerant rats or the induction of the hepatic mixed function oxidase activity. These results suggest that brain ACh plays an important role in the development and maintenance of tolerance to the central depressant effects of barbiturates.

PubMedSearch : Brezenoff_1976_Eur.J.Pharmacol_37_125
PubMedID: 1278236

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Citations formats

Brezenoff HE, Mycek MJ (1976)
Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3
European Journal of Pharmacology 37 :125

Brezenoff HE, Mycek MJ (1976)
European Journal of Pharmacology 37 :125