Extracellular GABA in globus pallidus increases during the induction of oral tremor by haloperidol but not by muscarinic receptor stimulation.
Tremulous jaw movements in rats can be induced by several conditions associated with parkinsonism and tremorogenesis, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Previous research indicates that neostriatal mechanisms are involved in the generation of tremulous jaw movements, but the striatal output pathways involved in these movements remain uncertain. One important pathway for striatal output is the GABAergic striatopallidal system. The present studies were undertaken to determine if extracellular levels of GABA in globus pallidus are associated with the induction of tremulous jaw movements by either a dopamine D2 antagonist (haloperidol) or a cholinomimetic (the muscarinic agonist pilocarpine). The first experiment studied the effects of both acute and repeated (i.e. 8 days) administration of the D2 antagonist haloperidol. In the second experiment, the effect of acute administration of the muscarinic agonist pilocarpine on GABA levels in the globus pallidus was examined. In both experiments, behavioral observations of tremulous jaw movements were conducted in parallel with the collection of microdialysis samples. Acute and repeated haloperidol treatment induced tremulous jaw movements, and significantly elevated extracellular GABA in globus pallidus. Pooling across all treatment groups, there was a significant positive correlation between pallidal GABA levels and the number of tremulous jaw movements induced during the first three samples collected after injection. However, injection of 4.0mg/kg pilocarpine had no effect on pallidal GABA release, despite the robust induction of tremulous jaw movements. These results indicate that the tremulous jaw movements induced by dopamine D2 antagonism and those induced through muscarinic receptor stimulation may be generated via distinct mechanisms.
Division of Behavioral Neuroscience, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Lyndsey E
LE
Collins-Praino
Samantha J
SJ
Podurgiel
Rotem
R
Kovner
Patrick A
PA
Randall
John D
JD
Salamone
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005917:Globus Pallidus / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D007568:Jaw / Q000187:drug effects; D008297:Male; D009068:Movement / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014202:Tremor / Q000139:chemically induced*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol; D004298:Dopamine