title: Stimulation of 5-hydroxytryptamine (5-HT(2C) ) receptors in the ventrotegmental area inhibits stress-induced but not basal dopamine release in the rat prefrontal cortex.
abstract: The present study investigated whether 5-HT(2C) receptors in the ventrotegmental area and prefrontal cortex regulate basal and stimulus-evoked dopamine release in the prefrontal cortex. Using the in vivo microdialysis technique in conscious rats, we studied the effect of a selective 5-HT(2C) receptor agonist, Ro60-0175, on basal and immobilization stress-induced dopamine release in the prefrontal cortex. Ro60-0175 intraperitoneally (2.5 mg/kg) and into the ventrotegmental area (10 microg/0.5 microL) completely antagonized the effect of stress on extracellular dopamine without altering basal levels. Infusion of 10 microm Ro60-0175 through the cortical probe had no significant effect on basal and stress-induced dopamine release. SB242084 (10 mg/kg), a selective antagonist of 5-HT(2C) receptors, significantly increased basal extracellular dopamine and completely prevented the effect of intraperitoneal and intraventrotegmental Ro60-0175 on the stress-induced rise of extracellular dopamine, but had no effect itself in stressed rats. The results show that Ro60-0175 suppresses cortical dopamine release induced by immobilization stress through the stimulation of 5-HT(2C) receptors in the ventrotegmental area. While confirming that endogenous 5-HT acting on 5-HT(2C) receptors tonically inhibit basal dopamine release in the prefrontal cortex, the present findings suggest that the stimulation of 5-HT(2C) receptors with an exogenous agonist preferentially inhibit stimulated release.
authors.affiliation: Mario Negri Institute of Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pozzi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Acconcia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ceglia
authors.forename: Roberto W
authors.initials: RW
authors.lastname: Invernizzi
authors.forename: Rosario
authors.initials: R
authors.lastname: Samanin
mesh_terms: D000631:Aminopyridines / Q000008:administration & dosage; D000818:Animals; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004333:Drug Administration Routes; D005021:Ethylamines / Q000008:administration & dosage; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012149:Restraint, Physical; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D005021:Ethylamines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C103848:Ro 60-0175; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D004298:Dopamine