title: GABAergic modulation of striatal peptide expression in rats and the alterations induced by dopamine antagonist treatment.
abstract: GABAergic modulation of enkephalin, substance P and glutamic acid decarboxylase (GAD67) gene expression and the alterations induced by dopamine receptor blockade were studied in the rat striatum. Following subchronic treatment with the GABA-A agonist muscimol, the GABA-B agonist baclofen or the GABA transaminase inhibitor gamma-vinyl GABA there were no significant changes in striatal peptide and GAD67 gene expression. Following repeated administration of the D-2 antagonists, eticlopride and haloperidol, there was an increase in enkephalin and GAD67 mRNA levels and parallel decrease in that of substance P. These were unaffected by co-administration of gamma-vinyl GABA. The D-1 antagonist, SCH 23390 administered alone or together with gamma-vinyl GABA did not alter peptide or GAD67 mRNA levels. It seems that pharmacological stimulation of GABA receptors has little effect on enkephalin, substance P or GAD67 mRNA expression in striatal output neurons.
authors.affiliation: Neurodegenerative Diseases Research Centre, King's College, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Jolkkonen
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: C D
authors.initials: CD
authors.lastname: Marsden
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology; D013373:Substance P / Q000096:biosynthesis* / Q000235:genetics; D015320:Tachykinins / Q000096:biosynthesis / Q000235:genetics; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D018079:Receptors, GABA; D012457:Salicylamides; D015320:Tachykinins; C044206:preprotachykinin; D009118:Muscimol; D013373:Substance P; D005680:gamma-Aminobutyric Acid; C033660:preproenkephalin; D005968:Glutamate Decarboxylase; D020888:Vigabatrin; D001418:Baclofen; D006220:Haloperidol; C045989:eticlopride