Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin(2C) receptors

Previous studies of conventional tricyclic and non-tricyclic antidepressant s have suggested that a number of these drugs display considerable pharmaco logical activity at 5-HT2C receptors in the brain. There:ls evidence that 5 -HT2C receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 1 0 mg/kg i.p.) and of the atypical antidepressant mianserin (2.5 mg/kg and 5 mg/kg i.p.) were studied on the extracellular concentration of dopamine (D A) in the nucleus accumbens of chloral hydrate-anesthetized rats, using int racerebral microdialysis. Amitriptyline and mianserin significantly increas ed DA release (+31.1+/-7.9% and +33.6+/-4.3%, respectively) at the higher d oses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyl ine (5 mg/kg i;p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p .), a selective 5-HT2C receptor agonist, on DA release. The effect of RO 60 -0175 (1 mg/kg i.p.) was completely blocked by SE 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT2C receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the n ucleus accumbens by blocking 5-HT2C receptors.