Increased catecholamine levels in specific brain regions of a rat model ofdepression: normalization by chronic antidepressant treatment

Alterations in catecholamine levels and neurotransmission have been shown i n depressive disorders. However, the exact sites of alterations and the rel ation between these alterations to the etiology of the disease and the effe ctiveness of antidepressant therapy are poorly understood. in this study, c atecholamine levels and metabolism were measured in specific brain regions of a genetic rat model of depression [Flinders Sensitive Line (FSL) rats], and compared to normal Sprague-Dawley rats. Norepinephrine levels were foun d to be two to threefold higher in the nucleus accumbens, prefrontal cortex , hippocampus and median raphe nucleus of FSL rats as compared with control Sprague-Dawley rats. Dopamine levels were sixfold higher in the nucleus ac cumbens and twofold higher in the striatum, hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley rats. After chronic treat ment with the antidepressant desipramine, the immobility score in a swim te st, as a measure of a behavioral deficit, as well as catecholamine levels o f the FSL rats became normalized, but these parameters in the control rats did not change. The results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased catecholamine lev els in specific brain sites, and further suggest the FSL rats as a model fo r elucidation of the molecular mechanism of clinically used antidepressant drugs. (C) 1999 Elsevier Science B.V. All rights reserved.