Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT(2C) receptors in the brain. There is evidence that 5-HT(2C) receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 10 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 (DA) in the nucleus accumbens of chloral hydrate- anesthetized rats, using intracerebral microdialysis. Amitriptyline and mianserin significantly increased DA release (+31.1±7.9% and +33.6±4.3%, respectively) at the higher doses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyline (5 mg/kg i.p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p.), a selective 5-HT(2C) receptor agonist, on DA release. The effect of RO 60-0175 (1 mg/kg i.p.) was completely blocked by SB 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT(2C) receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT(2C) receptors.
Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: Possible involvement of serotonin(2C) receptors
Di Giovanni G.;
2000-01-01
Abstract
Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT(2C) receptors in the brain. There is evidence that 5-HT(2C) receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 10 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 (DA) in the nucleus accumbens of chloral hydrate- anesthetized rats, using intracerebral microdialysis. Amitriptyline and mianserin significantly increased DA release (+31.1±7.9% and +33.6±4.3%, respectively) at the higher doses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyline (5 mg/kg i.p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p.), a selective 5-HT(2C) receptor agonist, on DA release. The effect of RO 60-0175 (1 mg/kg i.p.) was completely blocked by SB 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT(2C) receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT(2C) receptors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
