The learned helpless rat is considered to be one of the better animal models of depression. A genetically inbred strain with a high vulnerability to develop helplessness (LH), as well as a highly resistant strain (NLH) have both been developed. Since the brain peptide neuropeptide Y (NPY) is involved in the regulation of a number of behaviors known to be altered in clinical depression as well as in learned helplessness, we measured the relative level of NPY mRNA in the hippocampus and cortex of control Sprague Dawley (SD), LH and NLH rats. We find that NLH rats have approximately a 30-35% decrease in basal hippocampal NPY mRNA compared with SD and LH rats. By contrast, cortical NPY mRNA and hippocampal pre-proenkephalin and somatostatin mRNA levels were not significantly different in the 3 strains. The data suggest that the regulation of NPY gene expression may be involved in the reduced vulnerability of NLH rats to develop learned helplessness.
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