title: Dramatic increase in nigral t-[35S]butylbicyclophosphorothionate binding sites elicited by the degeneration of the striato-nigral GABAergic pathway: reversal by diazepam.
abstract: In rats, the degeneration of the striato-nigral GABAergic pathway caused by the intrastriatal injection of kainic acid induced a marked decrease (65%) of GABA content and glutamic acid decarboxylase (GAD) activity and a dramatic increase (225%) in the binding of t-[35S]butylbicyclophosphorothionate [( 35S]TBPS) to a membrane preparation from the substantia nigra homolateral to the injected striatum. The increase in [35S]TBPS binding in the denervated substantia nigra was exclusively due to an increased density of binding sites (Bmax) with no change in the dissociation constant (kd). The enhancement in [35S]TBPS binding was almost completely reversed by the intraperitoneal administration of diazepam (3 mg/kg) to kainic acid-lesioned rats. Moreover, diazepam produced a significant decrease (30%) in the density of [35S]TBPS binding sites also in the sham-operated side. In contrast the 'in vitro' addition of the GABAA receptor antagonist bicuculline (1 microM) to the membrane preparation from the denervated substantia nigra further increased [35S]TBPS binding. These findings suggest the view that the increase of nigral [35S]TBPS binding is directly related to the inhibition in the function of nigral GABAergic synapses following the loss of the striato-nigral GABAergic pathway. Our results indicate that [35S]TBPS binding to brain structure is a potential tool to reveal alteration in the function of GABAA receptor complex elicited by physiological, pharmacological and pathological conditions.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Sanna
authors.forename: M
authors.initials: M
authors.lastname: Serra
authors.forename: S
authors.initials: S
authors.lastname: Pepitoni
authors.forename: G
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; D003975:Diazepam