In:
Journal of Neurochemistry, Wiley, Vol. 91, No. 4 ( 2004-11), p. 852-859
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.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2004.91.issue-4
DOI:
10.1111/j.1471-4159.2004.02763.x
Language:
English
Publisher:
Wiley
Publication Date:
2004
detail.hit.zdb_id:
2020528-4
SSG:
12
