Involvement of the noradrenergic (NE) systems in development of barbiturate tolerance

B. Tabakoff, J. Yanai, R. F. Ritzmann

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1 Scopus citations

Abstract

C57BL/6 male mice were fed LAB Chow containing sodium phenobarbital (PhB). After consuming the PhB-containing diet for 6 or 8 days, mice showed a characteristic withdrawal syndrome when PhB was removed from the diet. The syndrome consisted of tremors, spontaneous clonic, tonic convulsions and significant hypothermia. Since tolerance to ethanol was shown to be dependent on the integrity of NE systems in brain, the authors injected animals with 6-hydroxydopamine (6-OHDA, 50 μg/mouse, icv) prior to chronic feeding with PhB and monitored signs of physical dependence and tolerance as described above. 6-OHDA injection resulted in a 58% depletion of brain NE, but did not significantly affect 5-HT and DA levels. Dependence and metabolic tolerance, which developed after 6 days of B consumption, were not significantly affected by 6-OHDA treatment. However, CNS tolerance was significantly less in 6-OHDA pretreated animals. Thus, the destruction of NE systems of brain hinders the development of tolerance to B as it does tolerance to ethanol.

Original languageEnglish
Pages (from-to)115-116
Number of pages2
JournalBehavior Genetics
Volume8
Issue number1
StatePublished - 1978
Externally publishedYes

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