BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF DIZOCILPINE IN THE OLFACTORY BULBECTOMIZED RAT MODEL OF DEPRESSION

The activity of dizocilpine (MK-801; 0.1 and 0.3 mg/kg) administered o nce daily intraperitoneally (IP) was assessed in the olfactory bulbect omized rat model of depression. Olfactory bulbectomy (OB) is associate d with a variety of behavioural abnormalities, such as hyperactivity i n the ''open field'' test. Previous studies have shown that chronic ad ministration of antidepressants can reverse this behavioural deficit. In the present study, chronic treatment with 0.1 and 0.3 mg/kg of dizo cilpine (IP) antagonized the lesion-induced hyperactivity in the ''ope n field'' test. Acute treatment with dizocilpine was associated with a n increase in locomotor activity in both sham-operated and OB rats, wi th a greater response in the sham-operated group. Following chronic tr eatment, this hyperactivity was found to be greater in the OB-treated animals compared with the sham-treated animals. olfactory bulbectomy r educed serotonin (5-HT), noradrenaline (NA), and dopamine (DA) concent rations in the frontal cortex. Chronic dizocilpine administration did not alter the 5-HT or NA response. In contrast, chronic administration of dizocilpine to OB animals did attenuate the OB-related deficit in DA. In the OB-operated control animals, there was an increase in DOPAC levels. In conclusion, chronic dizocilpine administration displays an tidepressant-like activity in the OB rat model of depression. However, unlike conventional antidepressants, dizocilpine does not correct the 5-HT and NA neurotransmitter deficits occur in this model. (C) 1997 E lsevier Science Inc.