Abstracts

Rationale: The adult Ts65Dn mutant mouse (Ts), a mouse model of Down syndrome (DS) is highly suceptible to γ-hydrohybutyrolactone (GBL) and the specific GABAB receptor agonist Baclofen. Both, GBL and BAC produced clusters of acute epileptic extensor spasms (AEES), which are amenable of quantification, pharmacological intervention and behavioural analyses (Snead et al Neurology 2007: 68(12)Sup1: pp A211; Cortez et al Neurology 2007: 68(12)Sup1: pp A211; Stewart et al, Behav Genet 2007 Mar;37(2):388-98). The was a differential effect of ACTH treatment in the Ts65Dn-GBL model (Trepanier et al. SfN 2007). Infantile spasms are highly prevalent during the first year of life, with a mean age of 6 months. Therefore, it is required to investigate the age specificity of the Ts65Dn-GBL model of acute epileptic extensor spasms (AEES) during the first week of rodent life and furthermore, the response to vigabatrin (GVG) treatment.Methods: Breeding, genotyping and continuous monitoring of 1 week old Ts65Dm mice (n= 6) and controls (n= 6), before and after i.p. treatment with GBL 50, 100, 200 mg/Kg, the specific GABAB receptor agonist Baclofen (BAC 0.5,1,2 mg/Kg), and 5-HTP (50, 100 mg/Kg). Results: Clusters of AEES were video captured in the GBL and BAC and 5-HTP groups. AEES were associated with electrodecremental response (EDR) on the ECoG. There was a reduction of EDR and AEES with GVG (n=4). The response to GVG was comparable to that obtained with ACTH 1-24 and the GABAB receptor antagonist CGP 35348. The were however residual AEES after GVG treatment which were slower and less frequent. There was a significant worsening of AEES and EDR on BAC and 5-HTP (p< 0.05, One Way ANOVA).Conclusions: The Ts65Dn model of acute epileptic extensor spasms (AEES) is reproducible in one week old Ts65Dn mice. Further investigation on the GABAB and 5-HTP mediated mechanisms in the generation of AEES is warranted. The Ts65Dn model is a valuable tool for the investigation of the differential response to ACTH and Vigabatrin treatment.