The influence of group III metabotropic glutamate receptor stimulation by (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid on the parkinsonian-like akinesia and striatal proenkephalin and prodynorphin mRNA expression in rats.
Group III metabotropic glutamate receptors (mGluRs) are widely distributed in the basal ganglia, especially on the terminals of pathways which seem to be overactive in Parkinson's disease. The aim of the present study was to determine whether (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-1), an agonist of group III mGluRs, injected bilaterally into the globus pallidus (GP), striatum or substantia nigra pars reticulata (SNr), can attenuate the haloperidol-induced catalepsy in rats, and whether that effect was related to modulation of proenkephalin (PENK) or prodynorphin (PDYN) mRNA expression in the striatum. Administration of ACPT-1 (0.05-1.6 microg/0.5 microl/side) caused a dose-and-structure-dependent decrease in the haloperidol (0.5 mg/kg i.p. or 1.5 mg/kg s.c.)-induced catalepsy whose order was as follows: GP>striatum>SNr. ACPT-1, given alone to any of those structures, induced no catalepsy in rats. Haloperidol (3 x 1.5 mg/kg s.c.) significantly increased PENK mRNA expression in the striatum, while PDYN mRNA levels were not affected by that treatment. ACPT-1 (3 x 1.6 microg/0.5 microl/side) injected into the striatum significantly attenuated the haloperidol-increased PENK mRNA expression, whereas administration of that compound into the GP or SNr did not influence the haloperidol-increased striatal PENK mRNA levels. Our results demonstrate that stimulation of group III mGluRs in the striatum, GP or SNr exerts antiparkinsonian-like effects in rats. The anticataleptic effect of intrastriatally injected ACPT-1 seems to correlate with diminished striatal PENK mRNA expression. However, since the anticataleptic effect produced by intrapallidal and intranigral injection of ACPT-1 is not related to a simultaneous decrease in striatal PENK mRNA levels, it is likely that a decrease in enkephalin biosynthesis is not a necessary condition to obtain an antiparkinsonian effect.
Konieczny
J
J
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Kraków, Poland. koniecz@if-pan.krakow.pl
Wardas
J
J
Kuter
K
K
Pilc
A
A
Ossowska
K
K
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003517:Cyclopentanes / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006220:Haloperidol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D018847:Opioid Peptides / Q000096:biosynthesis / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014233:Tricarboxylic Acids / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C108242:1-aminocyclopentane-1,3,4-tricarboxylic acid; D003517:Cyclopentanes; D018492:Dopamine Antagonists; D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D018847:Opioid Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D014233:Tricarboxylic Acids; C102718:metabotropic glutamate receptor 3; C029992:proenkephalin; D018698:Glutamic Acid; C033660:preproenkephalin; D006220:Haloperidol