The role of nigrostriatal dopamine in metabotropic glutamate agonist-induced rotation
Section snippets
Subjects
Male Sprague–Dawley rats (Harlan, Indianapolis, IN) weighing 175–275 g were used in all experiments. Rats were housed in a temperature/humidity controlled room on a 12 h:12 h light:dark cycle with access to food and water ad libitum.
Drugs
(R,S)-3,5-dihydroxyphenylglycine (DHPG), (2S,3S,4S)-CCG (L-CCG-I), l(+)-2-amino-4-phosphonobutyric acid (L-AP4) and 1-aminoindan-1,5-dicarboxylic acid (AIDA) (Tocris Cookson, St Louis, MO) were dissolved in 0.1 M phosphate buffer (PB) and pH was adjusted with 4 N NaOH.
Results
In acutely dopamine depleted rats, intrastriatal injection of DHPG resulted in no appreciable rotation (Table 1). In 6-OHDA lesioned rats, intrastriatal administration of the group I mGluR agonist DHPG induced contralateral rotation. However, the amount of rotation was lower than that induced in intact rats. The pharmacological profile of the rotation in 6-OHDA lesioned rats is similar to that seen in intact rats. The group I agonist DHPG induced contralateral rotation in a dose-dependent
Discussion
Our results show the differential effect of acute and chronic dopamine depletion on mGluR agonist-induced rotation at behavioral and functional neuroanatomical levels. Following unilateral, intrastriatal administration of DHPG, 6-OHDA lesioned rats show a significant level of rotation, although the magnitude is half that seen in intact rats. Acutely dopamine depleted rats show no significant level of rotation. Examination of FOS-LI, a presumed indicator of neuronal activity,6, 16and
Conclusions
The results presented here suggest that dopamine plays a permissive role in the generation of mGluR agonist-induced rotation, most likely due to increased dopamine release on the injected side. This asymmetrical increase in dopamine may serve to amplify fast excitatory neurotransmission through the basal ganglia on the injected side, ultimately resulting in increased motor output on the contralateral side of the body.
mGluRs have been suggested as useful targets for pharmacotherapy of
Acknowledgements
This work was supported by grants from The Lucille P. Markey Trust, The Michigan Parkinson Foundation, The Geriatrics Research Education and Clinical Center of the Ann Arbor VAMC, U.S. Public Health Service grants AG08671 and NS0722 and a VA Merit Grant to RLA. We thank Tim Desmond and Charles Rudick for technical assistance and Hannah Darcy of the Center for Statistical Consulting and Research, University of Michigan.
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