Increased striatal expression of glutamate decarboxylase 67 after priming of 6-hydroxydopamine-lesioned rats.
Previous single exposure (priming) to a dopamine receptor agonist greatly enhances the contralateral turning behaviour elicited by dopamine D1 receptor agonists in unilaterally 6-hydroxydopamine lesioned rats. In the present study we have investigated the levels of glutamate decarboxylase 67 and glutamate decarboxylase 65 messenger RNA in the striatum of 6-hydroxydopamine-lesioned rats primed with L-3,4-dihydroxyphenylalanine (L-DOPA) and challenged with the D1 receptor agonist SKF 38393, three days thereafter. As previously reported, levels of glutamate decarboxylase 67 messenger RNA increased in the striatum denervated by the 6-hydroxydopamine lesion as compared with the intact one. Striatal glutamate decarboxylase 67 messenger RNA levels, measured three days after priming with L-DOPA (50 mg/kg), further increased in the lesioned striatum while were not modified in the intact one. Administration of SKF 38393 (3 mg/kg) elicited a more intense contralateral turning behaviour in primed than in drug-naive 6-hydroxydopamine-lesioned rats but did not induce any change in striatal glutamate decarboxylase 67 messenger RNA. In contrast, striatal levels of glutamate decarboxylase 65 messenger RNA were not modified by either 6-hydroxydopamine lesions or priming with L-DOPA. The results show that priming with L-DOPA induces long-lasting changes in GABAergic neurons of the 6-hydroxydopamine-lesioned striatum. These changes might play a role in the increased behavioural response of striatal D1 receptors induced by priming.
Consolo
S
S
Mario Negri Institute of Pharmacological Research, Milano, Italy.
Morelli
M
M
Rimoldi
M
M
Giorgi
S
S
Di Chiara
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007839:Functional Laterality; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D005968:Glutamate Decarboxylase