NeuroAct Communication offers expert guidance to scientific communication.

  • Define a publication strategy: identify objectives, target audience, journals
  • Aid to effective presentation of pharmacological data
  • Experienced scientific writing and editing: research reports, posters, symposia

For more information Contact.
 

 

The central serotonin(2B) receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity.

Auclair AL, Cathala A, Sarrazin F, Depoortère R, Vincenzo Piazza P, Newman-Tancredi A, Spampinato U.
J Neurochem. 2010 Sep 1;114(5):1323-32. Epub 2010 Jun 7

Abstract The function of the serotonin(2B) receptor (5-HT(2B)R) in the mammalian brain is poorly characterised, 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 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 (NAc) was also observed after i.p. administration of 0.16 mg/kg RS 127445, another selective 5-HT(2B)R antagonist. In contrast, the 5-HT(2B)R agonist BW 723C86 (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 SB 206553 (5 mg/kg, i.p.) was unaltered by LY 266097 (0.63 mg/kg) pretreatment. 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 NAc, 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.Abstract The function of the serotonin(2B) receptor (5-HT(2B)R) in the mammalian brain is poorly characterised, 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 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 (NAc) was also observed after i.p. administration of 0.16 mg/kg RS 127445, another selective 5-HT(2B)R antagonist. In contrast, the 5-HT(2B)R agonist BW 723C86 (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 SB 206553 (5 mg/kg, i.p.) was unaltered by LY 266097 (0.63 mg/kg) pretreatment. 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 NAc, 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.