M. Zafer GÖREN, Rezzan AKER, Filiz ONAT, Aydan ERGÜN

THE EFFECTS OF PARTIAL BILATERAL LESIONING OF SUBSTANTIA NIGRA IN A GENETIC ABSENCE EPILEPSY RAT MODEL

Objective: "Genetic Absence Epilepsy Rats fromStrasbourg" (GAERS), an inbred Wistar strain,serve as an experimental venue. These ratsgenerate spontaneous spike-and-wavedischarges (SWD) and have increased yaminobutyricacid (GABA) levels in theventrolateral thalamus (VLT). Recently,substantia nigra pars reticulata (SNpr) wasreported to act as an endogeneous inhibitorymechanism in the generation, onset andmaintenance of various types of seizures. Thepresence of tonic control exerted by SNpr inabsence seizures should also be tested inGAERS.Methods: In this current study, GABA and Lglutamicacid release in VLT of GAERS withpartial bilateral electrolytic lesions of SNpr wasevaluated by using microdialysis technique withfluorescent detection.Results: GABA levels in VLT were 0.12±0.04 pMand 0.24±0.08 pM in sham-lesioned and SNprlesionedGAERS, respectively. L-glutamic acidlevel was found to be 0.415±0.150 pM in shamlesionedgroup and 0.324±0.094 pM in SNprlesionedGAERS. Statistical analysis revealed nosignificant difference between sham-lesionedand SNpr-lesioned rats. The number and theduration of SWD were also similar in two groups.Conclusion: These findings show that SNprdoes not exert a tonic control in GAERS and weassume that intact SNpr acts as a site that mayexert an inhibition on target structures whenactivated in GAERS.Key Words: GAERS (Genetic AbsenceEpilepsy Rats from Strasbourg), GABA (yaminobutyricacid), Substantia nigra,Ventrolateral thalamus, Absence epilepsy,Microdialysis, Nigral control of epilepsy.

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ladorola MJ, Gale li. Substantia nigra: site of anticonvulsant activity mediated by GABA. Science 1982; 218: 1237-1240.
Gale R. Mechanisms of seizure control mediated by gamma-aminobutyric acid: role of the substantia nigra. Fed Froc 1985; 44: 2414-2424.
Depaulis A, Vergnes M, Marescaux C Endogeneous control of epilepsy-the nigral output pathways in the inhibitory control of substantia nigra over generalized non- convulsive seizures in the rat. Neuroscience 1990; 39: 339-349.
Depaulis A, Vergnes M, Liu Z, hem pi Z, Marescaux C. Involvement of nigral control of epilepsy -the nigral inhibitory system. Frog Neurobiol 1994; 42: 33-52.
Löscher W, Czuczwar S, Jäckel R, Schwarz M. Effect of microinjections of y-vinyI GABA or isoniazid into substantia nigra on the
development of amygdala kindling in rats. Exp Neurol 1987; 95:622-638.
Depaulis A, Vergnes M, Marescaux C, Lannes B, Warier JM. Evidence that activation of GABA receptors in the substantia nigra supresses spontaneous spike and wave discharges in the rat. Brain Res 1988; 448:
-29.
Nauta WJfi, Domesick VB. Afferent and efferent relationships of the basal ganglia. ln:Evered and O'Connor M, eds. Functions of the basal ganglia. London: CIBA Foundation Symposium 107, Pitman, 1985:3-23.
Chevalier G, Vascher S, Deniali JM, Desban M. Disinhibition as a basic process in the expression of striatal functions-!. The striatonigral influence on tecto- spinal/tectodiencephalic neurons. Brain Res 1985:334: 215-226.
Oertel WH, Scmechel DE, Brownstein MJ, Tappaz ML, Ransom Dll, Roprin IJ . Decrease of glutamate decarboxylase (GAD)- immunoreactive nerve terminals In the substantia nigra after kainic acid lesion of striatum. J flistochem and Cytochem 1981; 29: 977-980.
Marescaux C, Vergnes M, Depaulis A . Genetic absence epilepsy rats from Strasbourg- a review. J Neural Transmission 1992; (Suppl. 35): 179-188.
Vergnes M, Marescaux C, Depaulis A, Micheletti G, Waiter JM . Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures. Exp Neurol 1987; 96: 127-136.
Liu Z, Marescaux C, Vergnes M, Depaulis A . Evidence for a critical role of GABA'ergic transmission within the thalamus in the genesis and control of absence seizures in the rat. Brain Res 1991; 45: 1-7.
Richards DA, Lemos T, Whitton FS, Bowery NG. Extracellular GABA in the ventrolateral thalamus of rats exhibiting absence epilepsy: a microdialysis study. J Neurochem 1995; 65(4): 1674-1680.
Faxinos G, Watson C. The rat brain in stereotaxic coordinates, 2nd edition, London: Academic Press, 1986; 29-44.
Obrenovitch TP, Richards DA, Sarna GS, Symon L. Combined intracerebral microdialysis and electrophysiological recording: methodology and applications. J Neurosci Methods 1995; 47: 139-145.
Biggs CS, Pearce BR, Fowler LJ, Whitton PS. The effect of sodium valproate on
Partial bilateral lesioning of substantia nigra
extracellular GABA and other amino acids in the rat ventral hippocampus: an in vivo microdialysis study. Brain Res 1992; 594: 138-142.
I 7. Smith S, Sharp T. Measurement of GABA in rat brain microdialysates using
ophtaldealdehyde-sulphite derivatization and high-performance liquid chromatography with electrochemical detection. J Chromatogr 1994; 652: 228-233.
Alexander G, Crutcher M. functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends neurosci 1990; 13: 266-271.
Deransart C, Vercueil L, Marescaux C, Depaulis A. The role of basal ganglia in the control of generalized absence seizures. Epilepsy Res 1998; 32: 213-223.
fallon JFt, Loughlin SE . Substantia nigra. In: Paxinos G, ed. The Rat nervous System, new York : Academic Press, 1995; 215-238.
tleimer L, Zahm D, Alheid G. Basal ganglia In: Paxinos G, eds. The Rat nervous System, new York : Academic Press, 1995: 579-628.
Morari M, Oconnor IVT, Ungerstedt U, Bianchi C, Fuxe R. Functional neuroanatomy of nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat. 2. Evidence for striatal n-methyl-D- aspartate receptor regulation of striatonigral gabaergic transmission and motor function, neuroscience 1996; 72: 89-97.
Shin C, Silver JM, Bonhaus DW, Mcnamara
JO. The role of substantia nigra in he development of kindling: pharmacologic and lesion studies. Brain Res 1987; 412: 311-
Goren MZ, Richards DA, Turner FI, Bowery nG. Extracellular GABA levels are increased in brain regions associated with the generation of absence seizures. Br J Pharmacol 1997; 122: 83P.
Corodimas KP, Rosenblat JS, Matthews TM, Morell Jl. neuroanatomical tract racing provides histological verification of neuron loss following cytotoxic lesion. J neurosci Methods 1994; 56: 71-75.