Formation of physical dependence on barbiturates and cerebral monoamines.

The effects of cerebral monoamine-related substances during the course of formation of barbital (B) dependence were studied in male S.D. rats by the B-admixed food method. The monoamine-related substances, p-chlorophenylalanine (PCPA), tranylcypromine (Tcp), alpha-methyl-p-tyrosine (alpha-MT), methamphetamine (MA) and reserpine were administered during each B treatment period, except in the control group that was fed a food admixed with B only. All groups were examined for B withdrawal signs during each of 2 B withdrawal periods. Compared with the control group, B withdrawal signs tended to be mild in the PCPA-treated group, remained similar in the Tcp-treated group, were severe in the alpha-MT-treated group, very mild in the MA-treated group, and very severe in the reserpine-treated group. These findings suggested B withdrawal signs may tend to be reduced in severity if the activity of catecholaminergic neurons is kept elevated during the course of formation of physical dependence on B, and they suggested that acquisition of tolerance to and formation of dependence on barbiturates tend to be reduced under a condition of reduced cerebral 5-HT activity.