title: Microdialysis and mass spectrometric monitoring of dopamine and enkephalins in the globus pallidus reveal reciprocal interactions that regulate movement.
abstract: 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 μM) 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 μM) 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 μM) 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.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Mabrouk
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Song
authors.forename: Robert T
authors.initials: RT
authors.lastname: Kennedy
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004743:Enkephalin, Leucine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; C534628:SCH 23390; D009270:Naloxone; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D000661:Amphetamine; D004298:Dopamine