1. ¹Department of Pharmacology, National University of Ireland, Galway, Galway, Ireland
2. ²School of Pharmacy and Pharmaceutical Sciences and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

Correspondence: Dr M Roche, Department of Pharmacology, National University of Ireland, University Road, Galway, Ireland. Tel:+353 91 493272; Fax:+353 91 494544; E-mail: michelle.roche@nuigalway.ie

Received 9 June 2006; Revised 18 September 2006; Accepted 29 September 2006; Published online 22 November 2006.

Abstract

The olfactory bulbectomized (OB) rat is a well-characterized animal model that exhibits a number of behavioral and neurochemical changes that have relevance to clinical depression. Hyperactivity in the open field is the most widely used parameter assessed in this model and is reversed following chronic, but not acute, antidepressant treatment. This study investigated OB-induced alterations in heart rate, body temperature, and neuronal activation following open-field exposure and the impact of chronic treatment with fluoxetine on these parameters. Upon placement in the open field, OB rats exhibited a characteristic hyperactivity response. Heart rate and body temperature were increased in sham-operated rats following open-field exposure, a predictable response to stress, which was significantly reduced in OB rats. Moreover bulbectomy reduced open field-induced cFOS expression in the basal nucleus of the stria terminalis while concurrently increasing expression in the hippocampus, amygdala, paraventricular nucleus of the thalamus, and dorsal raphe nucleus. Chronic fluoxetine treatment (10 mg/kg subcutaneous once daily for 5 weeks) attenuated all of these OB-associated changes. In conclusion, OB rats exhibit alterations in behavior, body temperature, heart rate, and neuronal activation in response to open-field exposure, which are reversed following chronic fluoxetine administration. These results identify stress-sensitive regions within the brain which are altered following bulbectomy and which may underlie the abnormal behavioral and physiological changes observed in this rodent model of depression.