Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats

Previous studies have demonstrated that chronic stress increases and antidepressant treatments decrease levels of tyrosine hydroxylase (TH) in locus coeruleus (LC). In the present study, the influence of chronic antidepressant treatment on the induction of TH immunoreactivity in response to cold stress is examined. It was found that chronic imipramine pretreatment (18 days) attenuated the induction of TH in response to cold stress, resulting in levels of TH immunoreactivity not different from control. In contrast, imipramine pretreatment for 1 or 7 days was not sufficient to normalize the stress-induced elevation of TH immunoreactivity. These findings raise the possibility that the therapeutic action of antidepressants may be derived, in part, from the ability of these treatments to normalize levels of TH and thereby the function of the NE neurotransmitter system under conditions of stress.