Neuropeptide Y in male and female brains of Flinders Sensitive Line, a rat model of depression. Effects of electroconvulsive stimuli.

Human and animal studies suggest that neuropeptide Y (NPY), a peptide co-localized and co-released with classical neurotransmitters, is involved in the pathogenesis of affective disorders. In addition, lithium, electroconvulsive treatments (ECT in humans and ECS in rodents) and antidepressants affect NPY in a specific temporal- and brain-region fashion. These results have been obtained on healthy male rats; females and/or "depressed" animals have essentially not been studied. Consequently, we studied brain NPY-like immunoreactivity (-LI) under basal conditions and following a series of ECS in both male and female Flinders Sensitive Line (FSL), an animal model of depression, and their controls, the Flinders Resistant Line (FRL) rats. Furthermore, we examined whether the oestrus cycle affects NPY-LI in these strains. Following sacrifice by focused microwave irradiation, the peptides were extracted from dissected brain regions and measured by radioimmunoassay. Hippocampal NPY-LI in both sexes was significantly lower in the "depressed" FSL compared to the control FRL. ECS increased NPY-LI in both male and female rats in both FSL and FRL strains in hippocampus, frontal cortex and occipital cortex. In the hypothalamus, the increase was found only in the FSL rats. In both FSL and control rats, the basal NPY-LI was lower in the hippocampus of female compared to male rats. NPY-LI did not vary during the different phases of the oestrus cycle. These results suggest that the gender differences are not due to NPY-LI variations during the oestrus. The results are consistent with our hypothesis that NPY plays a role in the pathophysiology of depressive disorders and provide further evidence that one of the modes of ECS action is to elevate NPY in the limbic system. Assumption that gender differences in NPY could explain increased rates of depression in women is speculative, but is in line with the findings in the present study.