Desipramine administration in the olfactory bulbectomized rat: changes in brain β‐adrenoceptor and 5‐HT2A binding sites and their relationship to behaviour

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Abstract
1 The effects of repeated administration of the tricyclic antidepressant drug, desipramine (DMI), on behaviour (locomotor activity and rearing) and the number and affinity of brain β-adrenoceptor and 5-HT2A receptor binding sites were examined in olfactory bulbectomized (OB) and sham-operated control rats. 2 Locomotor activity and rearing were increased in OB rats compared to sham-operated controls. The effect of various doses of DMI (administered orally twice daily for 21 days) on these behavioural measures was examined. A dose of 7.5 mg kg−1 provided optimal reversal of hyperlocomotion and increased rearing in OB rats, without changing these measures in sham-operated controls. 3 The time course of DMI (7.5 mg kg−1) on behavioural and neurochemical measures was examined. Locomotion and rearing in OB rats were not significantly altered after 7 days, were significantly attenuated after 14 days and were normalized after 21 days. 4 After 7 days of DMI administration the number of β-adrenoceptors was lower in frontal and occipital cortex and hippocampus. This reduction was largely restricted to the β1-adrenoceptor subtype. Administration of DMI for 14 or 21 days did not further reduce the number of β-adrenoceptors. The DMI induced reduction in β-adrenoceptors did not differ in OB and sham-operated control rats. 5 DMI administration for up to 21 days produced a progressive reduction in the number of 5-HT2A receptors in frontal cortex, without significant alterations in occipital cortex. 6 The time course of the reduction in the number of 5-HT2A receptors was similar to that of the DMI-induced behavioural changes whereas that for the reduction in β-adrenoceptors was clearly different. 7 The present results suggest that the action of DMI in this animal model is unlikely to be directly related to a reduction in β-adrenoceptors but may be related to a reduction in frontal cortical 5-HT2A receptors.