GABAB receptor activation exacerbates spontaneous spike-and-wave discharges in DBA/2J mice.
Rich evidence has highlighted that stimulation of gamma-amino-butyric acid (GABA)(B) receptors increases the occurrence of spike-and-wave discharges (SWDs), the electroencephalographic (EEG) landmark of absence epilepsy (AE). Recent findings suggest that the outcomes of GABA(B) activation in vivo are contingent on the chemical characteristics of the agonist. In particular, the endogenous ligand gamma-hydroxybutyrate (GHB) and its precursor gamma-butyro-lactone (GBL) have been shown to elicit different effects than the prototypical GABA(B) agonist baclofen. In view of these premises, the present study was aimed at the characterization of the effects of baclofen (0.5-10 mg/kg, i.p.) and GBL (5-100 mg/kg, i.p.) on the spontaneous SWDs and locomotor activity of DBA/2J mice. While both baclofen and GBL dose-dependently increased SWDs episodes, high doses of the latter (100 mg/kg, i.p.) reduced the occurrence of these phenomena and increased the number of isolated spikes. Interestingly, both compounds elicited a dose-dependent reduction of locomotor activity, in comparison with their vehicle-treated controls. The GABA(B) selective antagonist, SCH50911 (50 mg/kg, i.p.), reversed the changes in SWD occurrence and locomotion induced by baclofen and GBL, but failed to elicit intrinsic effects on either paradigm. These results indicate that GABA(B) receptor signaling might exert differential effects on SWDs in DBA/2J mice.
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, USA. bortolat@usc.edu
Marco
M
Bortolato
Roberto
R
Frau
Marco
M
Orrù
Mauro
M
Fà
Christian
C
Dessì
Monica
M
Puligheddu
Luigi
L
Barberini
Giuliano
G
Pillolla
Lorenzo
L
Polizzi
Federico
F
Santoni
Giampaolo
G
Mereu
Francesco
F
Marrosu
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000378:metabolism* / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D018080:Receptors, GABA-B / Q000378:metabolism*
D018755:GABA Agonists; D018080:Receptors, GABA-B; D001418:Baclofen