Protective effect of citalopram against the attenuation of the α1-potentiation of cAMP formation in Fischer 344 strain rats

Abstract We investigated the effects of citalopram, a selective serotonin reuptake inhibitor (SSRI), using an animal model for a depressive state. In Fischer 344 rats, known as emotional animals, repeated stress by twice-daily intraperitoneal (i.p.) saline injections for 14 days elicited a depressive state characterized by a decreased open-field activity and a prolonged immobility during the tail-suspension test. Concomitantly, suppression of norepinephrine (NE)induced CAMP formation was found in the cerebral cortical slices of the stress-exposed rats without changes in adrenergic α 1 - or β-receptors. The difference in cAMP formation between the intact and the stress groups was totally abolished under the blockade of the α 1 -receptor system or by the stimulation with isoproterenol or forskolin, whereas the suppressed response in the stress group was also observed in combination with isoproterenol and phenylephrine. From these results, we confirmed that the potentiation of the β-receptor-stimulated cAMP formation by the α 1 -receptor is attenuated following repeated stress. Chronic i.p. administration of citalopram dissolved in saline improved both the suppressed open-field activity and the prolonged immobility in the tail-suspension test. The animals treated with citalopram exhibited a comparable al -potentiation effect as observed in the intact rats. However, another SSRI, paroxetine, was less effective on the attenuation of the α 1 -potentiation in spite of its behavioral improvement in the depressive state. These findings suggest that citalopram has a protective effect against the repeated stress-induced depressive state by mechanisms besides the serotonin reuptake inhibition.