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The central serotonin 2B receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity
Author(s) -
Auclair Agnès L.,
Cathala Adeline,
Sarrazin Frédéric,
Depoortère Ronan,
Piazza Pier Vincenzo,
NewmanTancredi Adrian,
Spampinato Umberto
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06848.x
Subject(s) - chemistry , medicine , microdialysis , serotonin , endocrinology , agonist , dopamine , dopaminergic , pharmacology , receptor , biology
J. Neurochem. (2010) 114 , 1323–1332. Abstract The function of the serotonin 2B receptor (5‐HT 2B R) in the mammalian brain is poorly characterized, especially with regard to its influence on dopamine (DA) neuron activity. Here, we assessed this issue by evaluating effects of 5‐HT 2B Rs ligands in the control of striatal and accumbal DA outflow, using in vivo microdialysis in halothane‐anesthetized rats, and amphetamine‐induced hyperlocomotion in vigil rats. The selective 5‐HT 2B R antagonist 1‐[(2‐chloro‐3,4‐dimethoxyphenyl)methyl]‐2,3,4,9‐tetrahydro‐6‐methyl‐1H‐pyrido[3,4‐B]indole (LY 266097; 0.16 mg/kg, i.p.) had no influence on basal accumbal and striatal DA outflow but reduced significantly accumbal DA outflow when injected at 0.63 mg/kg. A significant reduction of basal DA outflow in the nucleus accumbens was also observed after i.p. administration of 0.16 mg/kg 2‐amino‐4‐(4‐fluoronaphth‐1‐yl)‐6‐isopropylpyrimidine, another selective 5‐HT 2B R antagonist. In contrast, the 5‐HT 2B R agonist α‐methyl‐5‐(2‐thienylmethoxy)‐1H‐indole‐3‐ethanamine (3 mg/kg, s.c.) had no influence on basal DA outflow in either brain region. The increase in striatal and accumbal DA outflow induced by the 5‐HT 2C R inverse agonist 5‐methyl‐1‐(3‐pyridylcarbamoyl)‐1,2,3,5‐tetrahydropyrrolo[2,3‐f] indole (5 mg/kg, i.p.) was unaltered by LY 266097 (0.63 mg/kg) pre‐treatment. Conversely, LY 266097 (0.63 mg/kg) significantly diminished the increase in DA outflow induced by haloperidol (0.01 mg/kg, s.c.) or amphetamine (0.5 mg/kg, i.p.) in the nucleus accumbens, but not in the striatum. Amphetamine‐induced hyperlocomotion (1 mg/kg) was also attenuated by LY 266097 (0.63 mg/kg). These findings demonstrate that 5‐HT 2B Rs exert a facilitatory control on mesoaccumbens DA pathway activity, and suggest that they may constitute a new target for improved treatment of DA‐related neuropsychiatric disorders.