Stimulation of 5‐hydroxytryptamine (5‐HT2C) receptors in the ventrotegmental area inhibits stress‐induced but not basal dopamine release in the rat prefrontal cortex

• Published in: Journal of neurochemistry 2002-07, Vol.82 (1), p.93-100
• Main Authors: Pozzi, Laura, Acconcia, Sabrina, Ceglia, Ilaria, Invernizzi, Roberto W., Samanin, Rosario
• Format: Article
• Language: English
• Subjects: 5‐hydroxytryptamine (5‐HT2C) receptors; Aminopyridines - administration & dosage; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine - analysis; Dopamine - metabolism; Drug Administration Routes; Ethylamines - administration & dosage; Extracellular Space - chemistry; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; immobilization stress; Indoles - administration & dosage; Male; Microdialysis; prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Restraint, Physical; Ro60–0175; SB242084; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Stress, Physiological - metabolism; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.00947.x

The present study investigated whether 5‐HT2C 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‐HT2C 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 µg/0.5 µL) completely antagonized the effect of stress on extracellular dopamine without altering basal levels. Infusion of 10 µm 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‐HT2C 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‐HT2C receptors in the ventrotegmental area. While confirming that endogenous 5‐HT acting on 5‐HT2C receptors tonically inhibit basal dopamine release in the prefrontal cortex, the present findings suggest that the stimulation of 5‐HT2C receptors with an exogenous agonist preferentially inhibit stimulated release.