Fluoxetine-induced increases in open-field habituation in the olfactory bulbectomized rat depend on test aversiveness but not on anxiety.

Little is known regarding the functional processes underlying the treatment efficacy of antidepressant drugs. Given the close association between stress, anxiety and depression, distinguishing the common and disparate features of these processes may contribute to our current understanding. Using the olfactory bulbectomized (OBX) rat, an animal model sensitive to a variety of antidepressant drugs, this study examined the effects of chronic fluoxetine administration on open-field behavior under different conditions of stressfulness (luminance) and compared the fluoxetine effects to those evoked by the anxiolytic lorazepam. Sham-operated and OBX rats received 21 daily injections of fluoxetine (10 mg/kg), one or seven injections of lorazepam (0.1 and 0.5 mg/kg) or vehicle prior to testing in the open field or plus maze. Time series data were collected and fit with exponential regression models to estimate behavioral reactivity, habituation and residual rate of responding. Relative to sham controls, OBX rats displayed increased locomotor activity in the high luminance open field but showed decreased activity in the lower luminance open field. Time series analysis revealed that while sham animals showed increased habituation in the high compared to lower luminance open field, OBX rats did not significantly modify their responding between the two conditions. Chronic fluoxetine treatment invoked rectifying effects in OBX animals only in the high luminance open field by increasing the rate of habituation. Both acute and subchronic administration of lorazepam also reduced OBX hyperactivity but did so only by decreasing the residual rate of responding. As expected, lorazepam administration significantly increased the ratio of open-to-total arm activity in the elevated plus maze. These findings suggest that OBX responding in the open field may be maladaptive, reflecting an inability to modify behavior appropriately in certain environmental contexts. Chronic antidepressant treatment enhances habituation of OBX animals only under more stressful or aversive conditions and appears to do so in a manner temporally distinct from anxiolytic treatment.