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Increased Response to Intrastriatal L(+)-2-Amino-4-Phosphonobutyrate (L-AP4) in Unilateral 6-Hydroxydopamine-Lesioned Rats

Unilateral intrastriatal injection of the prototype Group III metabotropic glutamate receptor agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4) induces rotation in rats with ipsilateral unilateral 6-hydroxydopamine lesions of the nigrostriatal projection but not in unlesioned control animals [Kearney et al., (1998) Neuroscience 87:881-891]. We studied differences in striatal neuron Fos-like immunoreactivity expression, striatal neuron Fos-like immunoreactivity localization, and regional [(14)C]-2-deoxyglucose uptake after unilateral intrastriatal injection of L-AP4 between control and unilateral 6-hydroxydopamine lesioned rats. There was a left shift of the dose response curve with more striatal neurons expressing Fos-like immunoreactivity at lower doses of L-AP4 in 6-hydroxydopamine lesioned animals. In unlesioned striata, L-AP4 injections tended to induce Fos-like immunoreactivity in striato-pallidal projection neurons. In lesioned animals, the majority of striatal neurons expressing Fos-like immunoreactivity were striatonigral projection neurons. In both control and lesioned animals, intrastriatal injection of L-AP4 produced widespread decreases in [(14)C]-2-deoxyglucose uptake in basal ganglia nuclei and related regions, but the magnitude of this effect increased markedly in lesioned animals. Striatal dopamine denervation enhances the response of striatal neurons to intrastriatally injected L-AP4 with an apparent shift in the type of striatal projection neuron responding to L-AP4.