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Volume 17, Number 11, Issue of June 1, 1997 pp. 4415-4425
Copyright ©1997 Society for Neuroscience

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [¹⁴C]-2-Deoxyglucose Autoradiographic Study

Received Jan. 30, 1997; revised March 13, 1997; accepted March 18, 1997.

Jennifer A. Feeley Kearney^{1, 3}, Kirk A. Frey^{1, 2, 3, 4}, and Roger L. Albin^{1, 3, 5}

¹ Neuroscience Program, ² The Mental Health Research Institute, and Departments of ³ Neurology and ⁴ Internal Medicine, Division of Nuclear Medicine, The University of Michigan, Ann Arbor, Michigan 48109, and ⁵ The Geriatrics Research, Education and Clinical Center, Veterans Administration Medical Center, Ann Arbor, Michigan 48105

Metabotropic glutamate receptors (mGluRs) are a major class of excitatory amino acid receptors. Eight mGluR subtypes, coupled to a variety of effector systems, have been cloned. These receptors have been classified into three groups based on amino acid sequence homology, effector systems, and pharmacological profile. Group I mGluRs increase phosphoinositide turnover, whereas groups II and III mGluRs are negatively coupled to adenylyl cyclase. The striatum possesses a high density of mGluR binding sites, and several mGluR mRNAs and proteins are expressed by striatal neurons. In rats, unilateral striatal injection of the nonsubtype selective mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) results in contralateral rotation with delayed onset, thought to be secondary to an increase in dopamine release. We sought to determine the mGluR subtype(s) involved, the modulation of the rotation by other basal ganglia neurotransmitter systems, and the functional anatomy underlying the rotational behavior. The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced contralateral rotation in a dose-dependent manner, whereas group II and group III agonists were ineffective. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by group I antagonists, but not by group II or group III antagonists. This suggests that the rotation is mediated by group I mGluRs. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by pretreatment with antagonists at muscarinic cholinergic, adenosine A₂, dopamine D₂, or dopamine D₁ receptors. Examination of FOS-like immunoreactivity after group I and group II mGluR agonist administration suggests increased activity in the striatopallidal pathway. However, [¹⁴C]-2-deoxyglucose uptake studies indicate increased activity in nuclei of the striatopallidal (indirect) pathway, particularly in the subthalamic nucleus, only after group I mGluR activation.

Key words: metabotropic glutamate receptor; basal ganglia; subthalamic nucleus; striatum; dopamine; adenosine A2 receptors; muscarinic receptors

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