Locomotor sensitization to cocaine in rats with olfactory bulbectomy

Olfactory bulbectomy in rats has been suggested as a comprehensive animal model of affective disorders associated with an array of behavioral changes, responsivity to chronic antidepressant treatment, and alterations in limbic structures thought to be critical in the pathophysiology of affective disorders. Recent work showing increased motivational responsivity to amphetamine suggests that olfactory bulbectomy could also be a useful animal model of dual diagnosis disorders. To further investigate this possibility, we studied locomotor activity in olfactory bulbectomized rats 14 days postsurgery in response to novelty and upon acute and repeated injections of cocaine (15/mg/kg) or saline. Consistent with prior studies, lesioned animals showed greater locomotor activity in response to a novel environment and significantly heightened locomotor activation upon initial cocaine exposure. Over 7 days of repeated cocaine injections, lesioned animals also showed a presensitized pattern of activity, with a loss of incremental increases in locomotion observed in control animals. Daily saline injections produced no group differences in pre- or postinjection activity, while cocaine-treated bulbectomized rats demonstrated a decline in their daily preinjection activity. These results suggest that neural alterations caused by olfactory bulbectomy produce altered behavioral response patterns to repeated doses of cocaine, and support the study of olfactory bulbectomy as a useful neurobehavioral model for understanding substance use disorder comorbidity in mental illness. (C) 2004 Wiley-Liss, Inc.