Original articleAltered Brain Activation Pattern Associated With Drug-Induced Attenuation of Enhanced Depression-Like Behavior in Rats Bred for High Anxiety
Section snippets
Animals
All animals tested were bred in the animal facilities of the Max Planck Institute of Psychiatry in Munich, Germany, as described previously (Landgraf and Wigger 2002). In brief, Wistar rats were selected and mated according to the results of an elevated plus maze test, to establish the lines termed HAB and LAB. Rats that spend < 5% or more than 50% in the open arms are considered as HABs or LABs, respectively. All offspring (including those used for the present study) are tested routinely at an
Results
The addition of paroxetine to the drinking water resulted in paroxetine plasma levels of 170 ± 14 ng/mL (n = 15) after a treatment period of 24 days and did not reduce the daily water intake of 8.5–9.5 ml/100g body weight. Paroxetine treatment did not significantly influence the weight gain of the rats, a result similar to that found in the study of Keck et al (2003). Weight at the start/end of treatment period: untreated HABs: 411 ± 13 g / 437 ± 9 g; paroxetine treated HABs: 409 ± 17 g / 440 ±
Discussion
The present data confirm behavioral findings from a previous study, in which chronic treatment with the clinically potent antidepressant paroxetine was effective in reducing the enhanced depression-like behavior of HAB rats in the forced swim test. We now additionally show that the behavioral effect of paroxetine was associated with a modulation of the swim stress-induced neuronal activation pattern in specific key areas, including limbic (prefrontal cortex, amygdala, bed nucleus of the stria
Conclusions
A major conclusion from these findings using an imaging method with cellular resolution is that an effective antidepressant drug treatment in an animal model of enhanced depression and anxiety affects neuronal responsivity in a rather restricted number (11 of 70) of specific, mainly limbic and hypothalamic, brain areas at different brain levels. It should be born in mind, however, that although c-Fos expression is a widely established marker of neuronal activation, neuronal firing might not
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