期刊
JOURNAL OF NEUROCHEMISTRY
卷 118, 期 1, 页码 24-33出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07293.x
关键词
amphetamine; dopamine; enkephalins; globus pallidus; mass spectrometry; microdialysis
资金
- National Institute on Drug Abuse [T32, DA07268]
- [R37 EB003320]
Pallidal dopamine, GABA and the endogenous opioid peptides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spectrometry and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pallidus. Amphetamine (3 mg/kg i.p.) evoked an increase in dopamine, GABA and methionine/leucine enkephalin. Local perfusion of the dopamine D-1 receptor antagonist SCH 23390 (100 mu M) fully prevented amphetamine stimulated enkephalin and GABA release in the globus pallidus and greatly suppressed hyperlocomotion. In contrast, the dopamine D-2 receptor antagonist raclopride (100 mu M) had only minimal effects suggesting a greater role for pallidal D-1 over D-2 receptors in the regulation of movement. Under basal conditions, opioid receptor blockade by naloxone perfusion (10 mu M) in the globus pallidus stimulated GABA and inhibited dopamine release. Amphetamine-stimulated dopamine release and locomotor activation were attenuated by naloxone perfusion with no effect on GABA. These findings demonstrate a functional relationship between pallidal dopamine, GABA and enkephalin systems in the control of locomotor behavior under basal and stimulated conditions. Moreover, these findings demonstrate the usefulness of liquid chromatography-mass spectrometry as an analytical tool when coupled to in vivo microdialysis.
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