Alterations in neuropeptide Y and Y1 receptor mRNA expression in brains from an animal model of depression: Region specific adaptation after fluoxetine treatment

To investigate the possible link between neuropeptide Y (NPY) and depression, we analyzed NPY and its receptors in different limbic-related regions in the Flinder sensitive line (FSL), a genetic animal model of depression. In situ hybridization histochemistry was used to measure mRNA expression levels of NPY and NPY receptors, Y1 and Y2, in the FSL as compared to the control Flinder resistant Line rats (FRL). In the FSL rats, NPY mRNA expression levels were significantly decreased in the nucleus accumbens and CA regions, but increased in the arcuate nucleus and anterior cingulate cortex. Y1 receptor mRNA expression was decreased in different cortical regions (retrosplenial, anterior cingulate, and occipital) and in the hippocampal dentate gyrus. Y2 mRNA expression levels did not differ between FSL and FRL animals. The effect of the antidepressant drug fluoxetine (a serotonin reuptake inhibitor) in the two rat strains was also studied. There was an increase of the NPY mRNA hybridization signal in the arcuate nucleus of both strains following the antidepressant treatment (10 μmol/kg; daily for 14 days). However, in other brain regions, fluoxetine administration caused a differential effect on the induction of NPY-related genes in the two rat strains: in the CA region and dentate gyrus NPY mRNA expression was increased in the FSL, but decreased in the FRL. In contrast, Y1 mRNA levels tended to be decreased by fluoxetine in the nucleus accumbens of the FSL rats, but increased in the FRL. These findings suggest an involvement of the Y1, but not the Y2, receptor subtype in depressive disorder. Overall, the results appear to sustain the importance of the FSL rats as an animal model of depression in view of the impairment of NPY genes and the ability of fluoxetine treatment to normalize NPY-related gene expression selectively in this strain.