Behavioural 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 once daily intraperitoneally (I.P.) was assessed in the olfactory bulbectomized rat model of depression. Olfactory bulbectomy (OB) is associated with a variety of behavioural abnormalities, such as hyperactivity in the "open field" test. Previous studies have shown that chronic administration of antidepressants can reverse this behavioural deficit. In the present study, chronic treatment with 0.1 and 0.3 mg/kg of dizocilpine (I.P.) antagonized the lesion-induced hyperactivity in the "open field" test. Acute treatment with dizocilpine was associated with an increase in locomotor activity in both sham-operated and OB rats, with a greater response in the sham-operated group. Following chronic treatment, this hyperactivity was found to be greater in the OB-treated animals compared with the sham-treated animals. Olfactory bulbectomy reduced serotonin (5-HT), noradrenaline (NA), and dopamine (DA) concentrations 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 antidepressant-like activity in the OB rat model of depression. However, unlike conventional antidepressants, dizocilpine does not correct the 5-HT and NA neurotransmitter deficits that occur in this model.
Redmond
A M
AM
Department of Pharmacology, University College Galway, Ireland.
Kelly
J P
JP
Leonard
B E
BE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism
D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D016291:Dizocilpine Maleate; D004298:Dopamine; D009638:Norepinephrine