Role of 5-HT1B receptors in entrainment disorder of Otsuka Long Evans Tokushima fatty (OLETF) rats

The role of 5-HT1A and 5-HT1B receptors in entrainment function was studied in Otsuka Long Evans Tokushima fatty (OLETF) rats and control Long Evans Tokushima Otsuka (LETO) rats. Light-induced (100 lux, 30 min) Fos expression in the suprachiasmatic nucleus was studied. Light-induced Fos expression was significantly decreased in OLETF rats compared to that in LETO rats. The decrease of light-induced Fos expression in OLETF rats was significantly reversed by pretreatment with the 5-HT1B receptor antagonist, isamoltan (3 mg/kg, i.p.). Simultaneous administration of CGS12066B (5 mg/kg, i.p.), a 5-HT1B agonist, blocked the reversal effect of isamoltan on Fos expression. Fos expression was not changed in LETO rats by pretreatment with isamoltan (3 mg/kg, i.p.). The Fos expression in LETO and OLETF rats was significantly decreased by pretreatment with the 5-HT1A antagonist, WAY-100,635. Phase shifts in locomotor activity paralleled the Fos expression. Light-induced phase shifts of locomotor activity in OLETF rats were significantly smaller than those in LETO rats. The phase shifts were significantly increased by isamoltan (3 mg/kg, i.p.) in OLETF rats. These results suggest that 5-HT1B receptors are involved in the reduced entrainment function of OLETF rats.