Effects of sertraline on regional neuropeptide concentrations in olfactory bulbectomized rats

Corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH) are two neuropeptides that exhibit increased cerebrospinal fluid (CSF) concentrations during major depressive episodes while somatostatin (somatotropin-release inhibiting factor, SRIF) is decreased. Clinical and basic research findings indicate that clinically effective antidepressant therapies often normalize the indicators of CRF and TRH hypersecretion as well as SRIF hyposecretion. The olfactory bulbectomized (OBX) rat is used to screen potential antidepressant drugs for clinical efficacy. This model requires chronic administration of the antidepressant drug to normalize OBX-induced behaviors such as increased locomotion in a novel environment. This report describes the regional brain concentration changes in CRF, TRH and SRIF produced by OBX and demonstrates the ability of the selective serotonin re-uptake inhibitor and antidepressant drug, sertraline (10 mg/kg), to normalize certain of these alterations in regional neuropeptide concentrations as well as normalizing OBX-induced increases in locomotor activity. OBX-induced increases in CRF concentrations in the hypothalamus and bed nucleus of the stria terminalis were specifically and significantly decreased by sertraline. OBX-induced increases in TRH concentrations in the hypothalamus were reversed by sertraline. The concentration of SRIF was significantly reduced by OBX in the anterior caudate and the piriform cortex, but sertraline reversed these changes only in the anterior caudate.