EFFECTS OF OLFACTORY BULBECTOMY ON NEUROPEPTIDE GENE-EXPRESSION IN THE RAT OLFACTORY LIMBIC SYSTEM/

Bilateral olfactory bulbectomy in the rat produces a well-characterize d syndrome that is independent of anosmia. This syndrome is reversed b y chronic antidepressant administration, which provides the basis for the olfactory bulbectomy model of depression. The present experiments Focused on neuropeptide plasticity in central olfactory/limbic structu res following olfactory bulbectomy in rats. Male Sprague-Dawley rats r eceived bilateral surgical ablation of the olfactory bulbs, sham surge ry, or no surgery and were killed either three, seven, 14 or 28 days l ater. Relative levels of messenger RNA encoding neuropeptide Y, somato statin, thyrotropin-releasing hormone, and corticotropin-releasing fac tor precursors in the forebrain were measured by quantitative in situ hybridization histochemistry using oligonucleotide probes. Prepro-neur opeptide Y messenger RNA levels in the piriform cortex and dentate gyr us were significantly elevated in bulbectomized rats 14 and 28 days af ter surgery compared to sham-operated and surgically naive rats. Prepr o-somatostatin messenger RNA levels in the piriform cortex were margin ally increased in bulbectomized rats at these time-points. Thyrotropin -releasing hormone and corticotropin-releasing factor precursor messen ger RNA levels were not altered in the brain regions studied. The resu lts indicate that olfactory bulbectomy causes long-term increases in t he expression of the neuropeptide Y gene. These findings suggest that neuropeptide Y plasticity in the olfactory/limbic system may contribut e to the olfactory bulbectomy syndrome in rats, and they provide furth er evidence of a role for neuropeptide Y in the pathophysiology of dep ression. (C) 1998 IBRO. Published by Elsevier Science Ltd.