Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

exert their therapeutic effects remain unknown. Responses to stressful stim uli are currently thought to contribute to the onset and course of affectiv e disorders. It has been postulated that antidepressants might act by ameli orating response patterns to challenging life events, such as processes of reactivity and/or habituation. Objective: Using the olfactory bulbectomy (O BX) rat model, this study examined the effects of various antidepressants o n measures of reactivity and habituation in behavioral tests assessing resp onses to novel stimuli. Methods: Sham-operated and OBX rats received 21 dai ly injections of fluoxetine (10 mg/kg), amitriptyline (10 mg/kg), desiprami ne (10 mg/kg), buspirone (3 mg/kg), or vehicle. Forty-eight hours after the last injection, animals were tested in the open field, elevated plus maze, and startle apparatus. For each test, time series data were collected and fit with exponential random effects models, in which estimated parameters a ssessed behavioral reactivity and habituation. Results: Relative to sham co ntrols, OBX rats displayed increased total locomotor activity in the open f ield and exhibited increased open arm behavior in the elevated plus maze. T hrough comparison with zinc sulfate-treated anosmic controls, these OBX-ind uced increases were attributed to both an augmentation of initial reactivit y due to anosmia and an attenuation of the average rate of habituation. Chr onic antidepressant treatment did not reduce the anosmia-related initial re activity levels of OBX rats to that of sham controls. Rather, the antidepre ssants evoked their restorative effects by increasing the rate of habituati on. Conclusions: These Findings suggest that antidepressants restore normal responding by permitting more effective adaptation to novel stimuli.