CHRONIC ANTIDEPRESSANT TREATMENTS INCREASE CYTOCHROME-B MESSENGER-RNALEVELS IN MOUSE CEREBRAL-CORTEX

Antidepressant therapies include drugs with a remarkable structural di versity and nonpharmacological interventions, such as electroconvulsiv e shock. Although the primary neurochemical effects of these treatment s may differ, the greater than or equal to 2- to 3-wk lag in therapeut ic onset has led to the hypothesis that adaptive changes in a final co mmon pathway are required for an antidepressant action. Based on this hypothesis, we sought to identify and characterize common changes in g ene expression following chronic antidepressant treatments. We utilize d a differential display strategy to identify genes that were differen tially expressed in mice following chronic treatment with imipramine a nd electroconvulsive shock. Differential display PCR followed by subcl oning, screening by reverse Northern blot, and confirmation by Norther n blot revealed a significant increase in the expression of one gene c andidate from mouse cortex following antidepressant treatments. The se quence of this 193-bp gene candidate was an exact match to the DNA seq uence of mouse mitochondrial cytochrome b. In contrast to the increase d mRNA levels of cytochrome b found in cortex, chronic treatment with these antidepressants did not alter mRNA levels in hippocampus, cerebe llum, or liver. Moreover, no differences in cortical levels of cytochr ome b mRNA were observed after either acute antidepressant treatments or chronic treatment with nonantidepressant drugs (haloperidol and mor phine). The observation that chronic, but not acute treatment with imi pramine and electroconvulsive shock produces a region-specific change in the levels of mRNA encoding cytochrome b suggests that this enzyme may be involved in the sequence of events resulting in an antidepressa nt action.