Effects of sertraline on regional neuropeptide concentrations in olfactorybulbectomized rats

Corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH ) are two neuropeptides that exhibit increased cerebrospinal fluid (CSF) co ncentrations during major depressive episodes while somatostatin (somatotro pin-release inhibiting factor, SRIF) is decreased. Clinical and basic resea rch findings indicate that clinically effective antidepressant therapies of ten normalize the indicators of CRF and TRH hypersecretion as well as SRIF hyposecretion. The olfactory bulbectomized (OBX) rat is used to screen pote ntial antidepressant drugs for clinical efficacy. This model requires chron ic administration of the antidepressant drug to normalize OBX-induced behav iors such as increased locomotion in a novel environment. This report descr ibes the regional brain concentration changes in CRF, TRH and SRIF produced by OBX and demonstrates the ability of the selective serotonin re-uptake i nhibitor and antidepressant drug, sertraline ( 10 mg/kg), to normalize cert ain of these alterations in regional neuropeptide concentrations as well as normalizing OBX-induced increases in locomotor activity. OBX-induced incre ases in CRF concentrations in the hypothalamus and bed nucleus of the stria terminalis were specifically and significantly decreased by sertraline. OB X-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 th ese changes only in the anterior caudate. (C) 2001 Elsevier Science Inc. Al l rights reserved.