The effect of focally administered drugs on self-stimulation of the ventral tegmental area in rats

An experiment was designed to test the hypothesis as advanced by Stein and Wise that self-stimulation has as its neural substrate a system of noradrenergic fibers originating in the ventral tegmental area and synapsing in the lateral hypothalamus, septal area and amygdala. Self-stimulation was measured using a shuttle task. Bipolar stimulating electrodes were placed in the ventral tegmental area of rats. In each subject a single cannula was implanted in one of the structures containing synapses of the putative fiber system. Three drugs, alpha-methyl-meta-tyrosine, imipramine and tranylcypromine were administered in a within-subjects design and the effects of drug administration on self-stimulation was determined. Order of drug presentation was counterbalanced in Latin-square fashion. It was found that none of the drugs using these procedures was interpreted as indicating that previously reported effects of the same drugs when administered systemically have been due to activity in parts of the central nervous system other than those structures studied here.