ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Little is known about the in vivo function of the GTP-binding protein-coupled “metabotropic” excitatory amino acid (EAA) receptor. In vitro studies on agonist-induced brain phosphoinositide hydrolysis have shown that (15,3i?)-1-aminocyclopentane-l,3-dicarboxylic acid is a highly selective and efficacious metabotropic EAA agonist. We have recently reported that in vivo unilateral intrastria-tal injection of (15′,3.K)-l-aminocyclopentane-l,3-dicar-boxylic acid induces transient extrapyramidal motor activation that manifests itself as contralateral turning. In this study, we fully characterized the onset of turning behavior following intrastriatal (1S,3.R)-1-aminocyclopentane-l,3-dicarboxylic acid injection and the possible involvement of striatal dopamine neurons in the mediation of this effect. Rats were anesthetized with the short-acting agent halo-thane to allow for rapid surgical recovery and thus early behavioral measurements. Intrastriatal (1S,3R)-1-aminocy-clopentane-l,3-dicarboxylic acid (1 μmol/2 μl) produced an incremental increase in contralateral turning starting at 1 h and plateauing 3–6 h after injection (peak effect, 39.1 ± 6.7 rotations per 5 min). Dopamine depletion with α-methyl-DL-p-tyrosine (250 mg/kg i.p., 80% depletion) resulted in 〉85% inhibition of (1S,3R)-1-aminocyclopentane-l,3-di-carboxylic acid-induced contralateral turning. The dopamine antagonist haloperidol (0.3 mg/kg i.p.) produced 48% inhibition of the (1S,3R)-1-aminocyclopentane-1,3-dicar-boxylic acid response. In time course studies, turning behavior correlated with increases in levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. These results suggest a functional interaction between the metabotropic EAA receptor and the dopami-nergic system in the striatum.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1992.tb08897.x
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