Effect of 8-OH-DPAT in the olfactory bulbectomized rat model of depression

The activity of the centrally active serotonin (5-HT) agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (1.0 mg kg^-1 twice daily, i.p. for 16 days), was assessed in two animal models of depression namely the forced swim test and on the hyperactive response of the olfactory bulbectomized (OB) rat in the 'open field'. The response to 8-OH-DPAT (0.15 mg kg^-1, s.c.) induced hypothermia in rats was also examined. In the forced swim test, acute treatment with 8-OH-DPAT (1.0 mg kg^-1, three applications in 24 h, test 60 min after the last application) significantly reduced the immobility time in both sham (P < 0.001) and OB (P < 0.01) groups. In the OB rat model, chronic treatment with 8-OH-DPAT (1.0 mg kg^-1) attenuated the OB-induced hyperactivity in the 'open field' (P < 0.05). The hypothermic response to 8-OH-DPAT (0.15 mg kg^-1, s.c.) was also attenuated after chronic 8-OH-DPAT (1.0 mg kg^-1) treatment in both sham and OB (P < 0.001) groups. It can be concluded that 8-OH-DPAT shows antidepressant-like activity in the forced swim test and OB rat model of depression probably due to activation of postsynaptic, and possibly to a lesser extent presynaptic, 5-HT(1A) receptors. In addition, chronic 8-OH-DPAT attenuated 8-OH-DPAT induced hypothermia presumably by causing 5-HT(1A) receptor subsensitization.