Microdialysis and mass spectrometric monitoring of dopamine and enkephalins in fhe globus pallidus reveal reciprocal interactions that regulate movement

摘要

Paflidal dopamine, GABA and the endogenous opioid pep-tides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spec-trometry and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pai-lidus. 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 muM) 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 pM) 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 pM) 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.