Effects of antidepressant drugs on the behavior of olfactory bulbectomized and sham-operated rats.

Abstract

Removal of the main olfactory bulbs in rats has been shown to alter neuronal function in brain areas involved in emotional regulation and homeostasis. These neuronal alterations result in maladaptive behavioral patterns and elevated plasma corticosterone that are suggestive of the symptom profile of patients with primary unipolar depression. Moreover, the endocrine and behavioral deficits of bulbectomized rats are reversed by the chronic administration of drugs that reverse the symptoms of depression in people when given chronically. However, the therapeutic improvements seen in patients with depression are not directly due to molecules of the antidepressant drug but rather to some relatively long-lasting compensatory change induced in the neuronal substrate by the drug. The present research demonstrates that the reversal of the olfactory bulb lesion deficits following chronic antidepressant drug administration in rats is not due to molecules of the drug per se but rather to some drug-induced change in the neuronal substrate that continues for at least 5 days after the last dose of drug. These endocrine, behavioral, and pharmacological similarities suggest that the study of rats with olfactory bulb ablation may make significant contributions to the understanding of the neuroscience of primary unipolar depression in humans.

Effect of the COX-2 Inhibitor Celecoxib on Behavioural and Immune Changes in an Olfactory Bulbectomised Rat Model of Depression

“…Moreover, those changes were reversed by chronic, but not acute, antidepressant treatments [3,8,10,[14][15][16][17][18] .…”

BIMT 17: a putative antidepressant with a fast onset of action?

“…The ablation of the olfactory bulbs induces many behavioural changes in the rat (Leonard 1984;Jesberger and Richardson 1986). The primary index of potential antidepressant activity is reversal of increased ambulation scores (Jancsar and Leonard 1983;Van Riezen and Leonard 1990).…”

Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat

“…Consequently, the OBX syndrome is believed to result from dysfunction in brainstem and limbic areas involving a variety of neurochemical and neuropharmacological changes affecting many different transmitter systems (Pohorecky et al 1969;Hirsh 1980;Janscar and Leonard 1984;Tiong and Richardson 1990;Gurevich et al 1993). Numerous studies have also demonstrated that many of the behavioral and biochemical alterations invoked by OBX are reversed by chronic administration of most antidepressant drugs (Van Riezen et al 1976;Cairncross et al 1978Cairncross et al , 1979aJesberger and Richardson 1986;Kelly et al 1997).…”

“…In the rat, olfactory bulbectomy (OBX) results in a characteristic behavioral phenotype, including disrupted circadian patterns in sleep (Sakurada et al 1976;Araki et al 1980), feeding (La Rue and LeMagnen 1972;Meguid et al 1993) increased irritability (Jesberger and Richardson 1986), and hyperactive responding in a novel, stressful environment (Marks et al 1971;Van Riezen and Leonard 1990;Giardina and Radek 1991). Many of these effects are not observed in animals rendered anosmic by destroying the olfactory receptor cells through irrigation of the nasal mucosa with zinc sulfate (ZnSO 4 ) (Alberts and Friedman 1972;Edwards 1974;Sieck and Baumbach 1974).…”