Effect of synthesis inhibition on the levels of brain catecholamines in barbital-dependent rats

Abstract

Adult male Sprague-Dawley rats were made barbital dependent by the long-term consumption of increasing concentrations of this compound in their drinking water. At the end of the drug regimen, the rats were sacrificed immediately or 1 or 2 days following barbital withdrawal. Some animals in each of these groups as well as control animals were treated with α methyl-para-tyrosine (250 mg/kg) (αMPT) or FLA-63 (40 mg/kg) 2 h before sacrifice. Following sacrifice, the telencephalon and brain stem of each animal were collected for subsequent analysis of dopamine (DA) and noradrenaline (NA) concentration. No changes in NA concentration were observed in either brain area of any of the experimental groups. On the other hand, when compared to the same parameter in control rats, the depletion of NA produced by αMPT or by FLA-63 pretreatment was significantly greater in the telencephalons of rats following 1 day of barbital withdrawal. Compared to control animals, the depletion of NA after FLA-63 pretreatment was also significantly greater in the brain stems of rats 1 and 2 days following barbital withdrawal. The concentration of DA in the telencephalons of drug-dependent rats was significantly decreased when compared to the levels in control animals by the second day of barbital withdrawal. The present data are consistent with an increase in utilization of brain NA and perhaps DA following the abrupt withdrawal of barbital from dependent rats. Further studies are required to determine if these changes in the brain catecholamines are a significant factor in the manifestation of the barbiturate abstinence syndrome.