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Modulation of dopamine release by striatal 5-HT2C receptors.
Synapse. 2005 Mar 15; 55(4):242-51.S

Abstract

Previous work has demonstrated that dopamine (DA) transmission is regulated by serotonin-2C (5-HT2C) receptors but the site(s) in the brain where these receptors are localized is not known. The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5-HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways. Microdialysis probes implanted in the striatum or the prefrontal cortex (PFC) measured dialysate DA concentrations, while the selective 5-HT2B/2C inverse agonist SB 206553 was given locally by reverse dialysis into these terminal regions. Additionally, the effects of the 5-HT2C agonist mCPP on striatal DA were measured. Local administration of SB 206553 (0.1-100 microM) into the striatum increased DA efflux in a concentration-dependent manner. Systemic administration of mCPP (1.0 mg/kg i.p.) decreased striatal DA and attenuated the SB 206553-induced increase. In contrast, infusion of SB 206553 (0.1-500 microM) by reverse dialysis into the PFC had no significant effect on basal DA efflux in this region. Additionally, high concentrations of SB 206553 had no effect on high potassium (K(+))-stimulated DA release in the PFC. These data contribute to a body of evidence indicating that 5-HT2C receptors inhibit nigrostriatal dopaminergic transmission. In addition, the results suggest that the nigrostriatal system is regulated by 5-HT2C receptors localized in the dorsal striatum. Elucidating the mechanisms by which serotonin (5-HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes such as schizophrenia, Parkinson's disease, anxiety, drug abuse, and/or depression.

Authors+Show Affiliations

Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15668911

Citation

Alex, Katherine D., et al. "Modulation of Dopamine Release By Striatal 5-HT2C Receptors." Synapse (New York, N.Y.), vol. 55, no. 4, 2005, pp. 242-51.
Alex KD, Yavanian GJ, McFarlane HG, et al. Modulation of dopamine release by striatal 5-HT2C receptors. Synapse. 2005;55(4):242-51.
Alex, K. D., Yavanian, G. J., McFarlane, H. G., Pluto, C. P., & Pehek, E. A. (2005). Modulation of dopamine release by striatal 5-HT2C receptors. Synapse (New York, N.Y.), 55(4), 242-51.
Alex KD, et al. Modulation of Dopamine Release By Striatal 5-HT2C Receptors. Synapse. 2005 Mar 15;55(4):242-51. PubMed PMID: 15668911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of dopamine release by striatal 5-HT2C receptors. AU - Alex,Katherine D, AU - Yavanian,Gregory J, AU - McFarlane,Hewlet G, AU - Pluto,Charles P, AU - Pehek,Elizabeth A, PY - 2005/1/26/pubmed PY - 2005/5/27/medline PY - 2005/1/26/entrez SP - 242 EP - 51 JF - Synapse (New York, N.Y.) JO - Synapse VL - 55 IS - 4 N2 - Previous work has demonstrated that dopamine (DA) transmission is regulated by serotonin-2C (5-HT2C) receptors but the site(s) in the brain where these receptors are localized is not known. The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5-HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways. Microdialysis probes implanted in the striatum or the prefrontal cortex (PFC) measured dialysate DA concentrations, while the selective 5-HT2B/2C inverse agonist SB 206553 was given locally by reverse dialysis into these terminal regions. Additionally, the effects of the 5-HT2C agonist mCPP on striatal DA were measured. Local administration of SB 206553 (0.1-100 microM) into the striatum increased DA efflux in a concentration-dependent manner. Systemic administration of mCPP (1.0 mg/kg i.p.) decreased striatal DA and attenuated the SB 206553-induced increase. In contrast, infusion of SB 206553 (0.1-500 microM) by reverse dialysis into the PFC had no significant effect on basal DA efflux in this region. Additionally, high concentrations of SB 206553 had no effect on high potassium (K(+))-stimulated DA release in the PFC. These data contribute to a body of evidence indicating that 5-HT2C receptors inhibit nigrostriatal dopaminergic transmission. In addition, the results suggest that the nigrostriatal system is regulated by 5-HT2C receptors localized in the dorsal striatum. Elucidating the mechanisms by which serotonin (5-HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes such as schizophrenia, Parkinson's disease, anxiety, drug abuse, and/or depression. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/15668911/Modulation_of_dopamine_release_by_striatal_5_HT2C_receptors_ L2 - https://doi.org/10.1002/syn.20109 DB - PRIME DP - Unbound Medicine ER -