Olfactory Bulb Ablation in the Rat: Behavioural Changes and Their Reversal by Antidepressant Drugs

Abstract

I The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2 Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3 Chronic pretreatment with amitriptyline (3 and 10mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4 Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5(+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both shamoperated and bulbectomized rats. 6 Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7 Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquisition of bulbectomized rats. 8 It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds.

Neurochemical and Behavioural Changes in Rat Models of Depression

“…10 Increased activity in an open field test is one of the quickest and most consistently reported behavioural changes in the OBX rats, 10,49,56 which does not occur as a consequence of the loss of smell. 42 The lesioning of the serotonergic projections to the olfactory bulb lesion (OB) with a local injection of the neurotoxin 5,7-dihydroxytrypramine (5,7-DHT) also produced hyperactivity in the open field test, which was also the case in OBX rats, 10,24 suggesting effects of the brain serotonergic system on the behavioural changes observed in the OBX rats. The hyperactivity was reversed by chronic administration of amitryiptyline and mianserine.…”

“…10 It was shown, more than three decades ago, that behavioural changes in olfactory bulbectomized (OBX) rats (e.g., hyperactivity, passive avoidance and irritability) were reversed following chronic antidepressant treatment. 42 The relationship…”

“…OBX rats showed a deficit in learning to avoid the foot shock by remaining on a platform that administers electrical shocks longer than the control group (passive avoidance test). 10,42 The neuronal pathways from the OB project directly to the anterior cortical nucleus of the amygdale. The amygdala modulates memory processing in other brain regions.…”

Role ofN-Methyl-D-aspartate Receptors in Antidepressant-Like Effects of σ1Receptor Agonist 1-(3,4-Dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine Dihydrochloride (SA-4503) in Olfactory Bulbectomized Rats

“…Chronic deprivation of olfaction, the primary sensory mode in rats, constitutes a stress of high intensity, and the behavioral deficits induced by OB are primarily the result of alterations in neuronal functions, which is supported by the phenomenon that the behavioral deficits can be reversed by antidepressant treatments although the olfactory bulbs are nonexistent (van Riezen et al, 1977;Jesberger and Richardson, 1988;Mar et al, 2000;O'Neil and Moore, 2003). The depression symptom-resembling deficits in OB rats can be normalized by chronic, not acute, antidepressant treatments (Jesberger and Richardson, 1985;Kelly et al, 1997).…”

PROCEEDINGS OF THE British Pharmacological Society

“…The results for the effects of bile duct ligation on sleeping times are shown in Figure 1 and it can be seen that they showed a significant rise in the ligated We have established that antidepressant drugs selectively reverse the effects of bilateral olfactory bulb ablation (van Riezen, Schnieden & Wren, 1977;Cairncross, Cox, Forster & Wren, 1977a) and have recently demonstrated that bilateral intrabulb injection of 5,6-dihydroxytryptamine (5,6-DHT, 8tig) produces similar behavioural and biochemical effects to bulbectomy (Cairncross, Cox, Forster & Wren, 1977b). We have now attempted to assess the susceptibility of the 5,6-DHT-induced syndrome to alteration by psychotropic drugs.…”