Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin2C receptors
by
Di Matteo V, Di Mascio M, Di Giovanni G, Esposito E
Istituto di Ricerche Farmacologiche Mario Negri,
Consorzio Mario Negri Sud,
Chieti, Italy
Psychopharmacology (Berl) 2000 May; 150(1):45-51
ABSTRACT
Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT2C receptors in the brain. There is 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 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-HT2C 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-HT2C receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT2C receptors.
LSD
SSRIs
5-HT2
5-HT3
5-HT4
5-HT2c
5-HT1a
5-HT2a
Serotonin
Dopamine
Mianserin
Amitriptiline
Agomelatine
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