TY - JOUR
T1 - Increased catecholamine levels in specific brain regions of a rat model of depression
T2 - Normalization by chronic antidepressant treatment
AU - Zangen, Abraham
AU - Overstreet, David H.
AU - Yadid, Gal
N1 - Funding Information:
This research was performed as part of A. Zangen's PhD thesis and supported by Bar-Ilan Research Foundation (no. 2520).
PY - 1999/4/10
Y1 - 1999/4/10
N2 - Alterations in catecholamine levels and neurotransmission have been shown in depressive disorders. However, the exact sites of alterations and the relation between these alterations to the etiology of the disease and the effectiveness of antidepressant therapy are poorly understood. In this study, catecholamine 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 found 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 accumbens and twofold higher in the striatum, hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley rats. After chronic treatment with the antidepressant desipramine, the immobility score in a swim test, as a measure of a behavioral deficit, as well as catecholamine levels of 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 levels in specific brain sites, and further suggest the FSL rats as a model for elucidation of the molecular mechanism of clinically used antidepressant drugs.
AB - Alterations in catecholamine levels and neurotransmission have been shown in depressive disorders. However, the exact sites of alterations and the relation between these alterations to the etiology of the disease and the effectiveness of antidepressant therapy are poorly understood. In this study, catecholamine 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 found 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 accumbens and twofold higher in the striatum, hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley rats. After chronic treatment with the antidepressant desipramine, the immobility score in a swim test, as a measure of a behavioral deficit, as well as catecholamine levels of 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 levels in specific brain sites, and further suggest the FSL rats as a model for elucidation of the molecular mechanism of clinically used antidepressant drugs.
KW - Antidepressant
KW - Catecholamines
KW - Dopamine
KW - Norepinephrine
KW - Turnover
UR - http://www.scopus.com/inward/record.url?scp=0033541514&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(99)01214-7
DO - 10.1016/S0006-8993(99)01214-7
M3 - Article
AN - SCOPUS:0033541514
SN - 0006-8993
VL - 824
SP - 243
EP - 250
JO - Brain Research
JF - Brain Research
IS - 2
ER -