Imipramine antagonism of the CNS effects of norepinephrine behavioral and biochemical correlates

Chicks (1–5 day-old) were made hyperactive and aggressive with the tricyclic antidepressant, imipramine hydrochloride. Norepinephrine (NE), which crosses the bloodbrain barrier to produce behavioral depression in the chick (in a monotonic, dose-response manner) antagonized the behavioral effects of imipramine. Associated with this behavioral antagonism was a relative decrease in the radioactivity of brain normetanephrine and 3-methoxy-4-hydroxymandelic acid when isotopic NE was infused following imipramine pretreatment. This suggests that imipramine may block the access of NE to the post-synaptic membrane as well as interfering with other aspects of NE inter- and intracellular mobility. The differences from the previous literature shown in this study may be due to species differences or the failure of other studies to achieve behavioral activation with imipramine before doing biochemical studies.