Exocytotic release of dopamine in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice.
The present study used voltammetry to ascertain whether electrically stimulated somatodendritic dopamine release in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice was due to exocytosis or dopamine transporter reversal, as has been debated. The maximal concentration of electrically evoked dopamine release was similar between ventral tegmental area slices from dopamine transporter knockout and C57BL/6 mice. Dopamine transporter blockade (10 microM nomifensine) in slices from C57BL/6 mice inhibited dopamine uptake but did not alter peak evoked dopamine release. In addition, dopamine release and uptake kinetics in ventral tegmental area slices from dopamine transporter knockout mice were unaltered by the norepinephrine transporter inhibitor, desipramine (10 microM), or the serotonin transporter inhibitor, fluoxetine (10 microM). Furthermore, maximal dopamine release in ventral tegmental area slices from both C57BL/6 and dopamine transporter knockout mice was significantly decreased in response to Na(+) channel blockade by 1 microM tetrototoxin, removal of Ca(2+) from the perfusion media and neuronal vesicular monoamine transporter inhibition by RO-04-1284 (10 microM) or tetrabenazine (10 and 100 microM). Finally, the glutamate receptor antagonists AP-5 (50 and 100 microM) and CNQX (20 and 50 microM) had no effect on peak somatodendritic dopamine release in C57BL/6 mice. Overall, these data suggest that similar mechanisms, consistent with exocytosis, govern electrically evoked dopamine release in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice.
John
Carrie E
CE
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, United States.
Jones
Sara R
SR
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D005089:Exocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013747:Tetrabenazine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D013779:Tetrodotoxin; D004298:Dopamine; D013747:Tetrabenazine