Brain Noradrenergic Systems as a Prerequisite for Developing Tolerance to Barbiturates

• DOI: 10.1126/science.565533
• Publication Date: 2006-10-05T16:35:25Z
• Authors: Boris Tabakoff; Joseph Yanai; Ronald F. Ritzmann
• Keywords: Male; 0301 basic medicine; Sympathetic Nervous System; Behavior, Animal; Substance-Related Disorders; Brain; Drug Tolerance; Biochemistry; Substance Withdrawal Syndrome; 3. Good health; Hydroxydopamines; Mice; Norepinephrine; 03 medical and health sciences; Strains:; Metabolism:; Phenobarbital; Reflex; Animals; Humans; Body Temperature Regulation

Mice treated with 6-hydroxydopamine before they were chronically fed phenobarbital did not develop functional barbiturate tolerance, measured by duration of the loss of righting reflex and hypothermia. Injection of 6-hydroxydopamine caused significant depletion of brain norepinephrine, while brain dopamine levels were not significantly depleted. Intact brain noradrenergic systems seem to be necessary for developing tolerance to the hypnotic and hypothermic effects of the barbiturates.