THE OLFACTORY BULBECTOMIZED RAT AS A MODEL OF DEPRESSION - AN UPDATE

The olfactory bulbectomized (OB) rat has been proposed as an animal mo del of depression The following behavioural changes have been observed following bilateral olfactory bulbectomy: hyperactivity in an enclose d arena, such as the open field; enhanced nocturnal hyperactivity in a 24-hr home cage activity monitor; deficits in memory, as shown by pas sive avoidance behaviour and in the Morris maze and the 8-arm radial m aze; increased open arm entries in the elevated plus-maze; and changes in food motivated and conditioned taste aversion behaviour. Alteratio ns in the noradrenergic, serotonergic, cholinergic, gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmitter systems are also associated with olfactory bulbectomy. The variety of immune changes fo llowing olfactory bulbectomy includes reduced neutrophil phagocytosis, lymphocyte mitogenesis, lymphocyte number and negative acute phase pr oteins, increased leucocyte adhesiveness/aggregation, monocyte phagocy tosis, neutrophil number and positive acute phase proteins. An enhance d nocturnal secretion of corticosterone is observed in OB rats, which is normally suppressed by dexamethasone The most commonly employed beh avioural indicator of antidepressant activity is attenuation of the OB -related hyperactivity in the open-field. However, many of the other b ehavioural, neurotransmitter and immune changes have been shown to be attenuated by chronic (but not acute) antidepressant treatment. Tricyc lic antidepressants (amitriptyline, desipramine), atypical agents (mia nserin), selective serotonin reuptake inhibitors (paroxetine, sertrali ne, fluvoxamine), reversible inhibitors of monoamine oxidase A (moclob emide), as well as putative antidepressants such as 5-hydroxytryptamin e(1A) agonists (zalospirone, ipsapirone), noncompetitive N-methyl-D-as partate antagonists (MK-801) and triazolobenzodiazepines (alprazolam, adinazolam), have demonstrated antidepressant-like activity in this mo del. As many of the changes exhibited by the OB rat are qualitatively similar to those observed in depressed patients, it may be concluded t hat the OB rat is a model of depression and not just a means whereby p utative antidepressants may be tested. (C) 1997 Elsevier Science Inc.