Behavioural and neuropharmacological properties of the dibenzazepines, desipramine and lofepramine: studies on the olfactory bulbectomized rat model of depression.

1. Lofepramine was compared with its major desipramine for its effects on adaptation to novel objects in the home cage (neophobia) and exploratory behaviours in both sham operated and olfactory bulbectomized rats. 2. In the test for neophobia (marble burying), the aversive response of bulbectomized rats differed from that of the sham operated animals, the bulbectomized rats showing a diminished aversive response. This response was unaffected by either antidepressant. 3. Of two tests for exploratory activity, the "open field" test clearly differentiated the bulbectomized rats treated with desipramine from those treated with lofepramine. In the lower doses used (1 and 10 mg/kg), only desipramine treatment significantly attenuated the hypermotility of the bulbectomized rats. In high doses (30 mg/kg), lofepramine also attenuated the hypermotility of the bulbectomized rats; this could have been due to the presence of high concentrations of the desipramine metabolite. In a non-stressful novel environment ('hole board'), neither drug significantly affected the behaviour of sham operated or olfactory bulbectomized rats. Neither antidepressant had noticeable anticholinergic properties as indicated by the number of faecal boli deposited. 4. Acute clonidine administration was found to attenuate the activity of rats in the 'open field' apparatus. This effect was attenuated following the chronic administration of desipramine but not lofepramine. It may be concluded that the pharmacological activity of lofepramine is independent of its metabolism to desipramine in vivo.