Tags

Type your tag names separated by a space and hit enter

Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release.
J Neurochem 2004; 91(4):852-9JN

Abstract

3,4,-Methylenedioxymethamphetamine (MDMA; 'ecstasy') acts at monoamine nerve terminals to alter the release and re-uptake of dopamine and 5-HT. The present study used microdialysis in awake rats to measure MDMA-induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell. (+)-MDMA (0, 2.5, 5 and 10 mg/kg, i.p.) increased GABA efflux in the VTA with a bell-shaped dose-response. This increase was blocked by application of TTX through the VTA probe. MDMA (5 mg/kg) increased 5-HT efflux in VTA by 1037% (p < 0.05). The local perfusion of the 5-HT(2B/2C) antagonist SB 206553 into the VTA reduced VTA GABA efflux after MDMA from a maximum of 229% to a maximum of 126% of basal values (p < 0.05), while having no effect on basal extracellular GABA concentrations. DA concentrations measured simultaneously in the NAC shell were increased from a maximum of 486% to 1320% (p < 0.05). The selective DA releaser d-amphetamine (AMPH) (4 mg/kg) also increased VTA GABA efflux (180%), did not alter 5-HT and increased NAC DA (875%) (p < 0.05), but the perfusion of SB 206553 into the VTA failed to alter these effects. These results suggest that MDMA-mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5-HT(2B/2C) receptors in the VTA.

Authors+Show Affiliations

Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15525339

Citation

Bankson, Michael G., and Bryan K. Yamamoto. "Serotonin-GABA Interactions Modulate MDMA-induced Mesolimbic Dopamine Release." Journal of Neurochemistry, vol. 91, no. 4, 2004, pp. 852-9.
Bankson MG, Yamamoto BK. Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release. J Neurochem. 2004;91(4):852-9.
Bankson, M. G., & Yamamoto, B. K. (2004). Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release. Journal of Neurochemistry, 91(4), pp. 852-9.
Bankson MG, Yamamoto BK. Serotonin-GABA Interactions Modulate MDMA-induced Mesolimbic Dopamine Release. J Neurochem. 2004;91(4):852-9. PubMed PMID: 15525339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release. AU - Bankson,Michael G, AU - Yamamoto,Bryan K, PY - 2004/11/5/pubmed PY - 2005/5/26/medline PY - 2004/11/5/entrez SP - 852 EP - 9 JF - Journal of neurochemistry JO - J. Neurochem. VL - 91 IS - 4 N2 - 3,4,-Methylenedioxymethamphetamine (MDMA; 'ecstasy') acts at monoamine nerve terminals to alter the release and re-uptake of dopamine and 5-HT. The present study used microdialysis in awake rats to measure MDMA-induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell. (+)-MDMA (0, 2.5, 5 and 10 mg/kg, i.p.) increased GABA efflux in the VTA with a bell-shaped dose-response. This increase was blocked by application of TTX through the VTA probe. MDMA (5 mg/kg) increased 5-HT efflux in VTA by 1037% (p < 0.05). The local perfusion of the 5-HT(2B/2C) antagonist SB 206553 into the VTA reduced VTA GABA efflux after MDMA from a maximum of 229% to a maximum of 126% of basal values (p < 0.05), while having no effect on basal extracellular GABA concentrations. DA concentrations measured simultaneously in the NAC shell were increased from a maximum of 486% to 1320% (p < 0.05). The selective DA releaser d-amphetamine (AMPH) (4 mg/kg) also increased VTA GABA efflux (180%), did not alter 5-HT and increased NAC DA (875%) (p < 0.05), but the perfusion of SB 206553 into the VTA failed to alter these effects. These results suggest that MDMA-mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5-HT(2B/2C) receptors in the VTA. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15525339/Serotonin_GABA_interactions_modulate_MDMA_induced_mesolimbic_dopamine_release_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0022-3042&amp;date=2004&amp;volume=91&amp;issue=4&amp;spage=852 DB - PRIME DP - Unbound Medicine ER -