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Abstract
Affective disorders and substance abuse frequently coexist, yet few previous studies have examined drug self-administration using animal models of depression. The present studies employed the olfactory bulbectomy rat model of depression. Bilateral olfactory bulbectomy produces behavioral, physiological and neurochemical changes that closely resemble depression symptomology. Bulbectomized, sham-operated, and anosmic control rats were given a choice between a 0.1 mg/ml d-amphetamine solution and distilled water for 3 days. Bulbectomized rats exhibited greater intake of amphetamine solution than sham-operated and anosmic rats. In vivo microdialysis of dopamine, DOPAC, and HVA in the ventral and dorsal striatum of bulbectomized and sham-operated rats was performed. Bulbectomized rats had significantly higher basal levels of dopamine than sham-operated controls. Differences between regions were not seen. Bulbectomized and sham-operated rats revealed no significant differences in dopamine, DOPAC, or HVA when dialysis samples were taken while an oral amphetamine solution was available. The results suggest that dysregulation of the mesolimbic dopamine system in bulbectomized rats leads to increased drug seeking behavior.