The neuronal nicotinic acetylcholine receptors alpha 4 and alpha 6 differentially modulate dopamine release in mouse striatal slices

• Published in: Journal of neurochemistry 2008-06, Vol.105 (5), p.1761-1769
• Main Authors: Meyer, Erin L, Yoshikami, Doju, McIntosh, J Michael
• Format: Article
• Language: English
• Subjects: Animals; Corpus Striatum - metabolism; Corpus Striatum - secretion; Dopamine - metabolism; Dopamine - secretion; Electric Stimulation; Evoked Potentials - genetics; Evoked Potentials - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Nicotinic - biosynthesis; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05266.x

Striatal dopamine (DA) plays a major role in the regulation of motor coordination and in the processing of salient information. We used voltammetry to monitor DA-release evoked by electrical stimulation in striatal slices, where interneurons continuously release acetylcholine. Use of the alpha6-selective antagonist alpha-conotoxin MII[E11A] and alpha4 knockout mice enabled identification of two populations of DA-ergic fibers. The first population had a low action potential threshold, and action potential-evoked DA-release from these fibers was modulated by alpha6. The second population had a higher action potential threshold, and only alpha4(non-alpha6) modulated action potential-evoked DA-release. Striatal DA-ergic neurons fire in both tonic and phasic patterns. When stimuli were applied in a train to mimic phasic firing, more DA-release was observed in alpha4 knockout versus wild-type mice. Furthermore, block of alpha4(non-alpha6), but not of alpha6, increased DA release evoked by a train. These results indicate that there are different classes of striatal DA-ergic fibers that express different subtypes of nicotinic receptors.