Abstracts

Rationale: Early postnatal administration of the cholesterol biosynthesis inhibitor AY-9944 (7.5 mg/Kg) to sucking rodents, leads to a life long disorder with chronic seizure activity characterized by 5-6 Hz slow spike and wave discharges, characteristic of chronic atypical absence seizures (CAAS) (Stewart et al, Epilepsy and Behavior 2006: 9: pp 564-572; Cortez MA, Snead OC III: Pharmacological models of generalized absence seizures in rodents. In: Chapter 10: Models of Seizures and Epilepsy (Pitkanen A, Schwartzkroin PA, Moshe SL, eds). Elsevier, San Diego, California 2006: pp 111-126). The AY- induced CAAS are also associated with behavioral changes that are characteristic of hyperactivity and stereotypy (Stewart et al, Epilepsy and Behavior 2006: 9: pp 564-572), and cognitive impairment (Chan et al, Eur J Pharmacology 2006: 541(1-2): pp 64-76).Methods: AY-treated male C3H mice (N=16) were weaned into environmentally enriched (EE) or non- enriched standard cages (NEE) for thirty days. The behavior of EE-AY mice (N=10) was compared to that of NEE-AY mice (N=6) using standard testing for open-field locomotion and olfactory recognition memory. Results: The EE-AY mice exhibited less behavioral hyperactivity during a 15-min open-field session as indicated by a decrease in total movements (576.87 ± 10.04 vs. 630 ± 13.83), as well as in episodes of rotational stereotypy (8.25 ± 1.05 vs. 18.85 ± 2.92), and jumping (3.81 ± 0.84 vs. 16.75 ± 8.45) (all P<.05, ANOVA). EE-AY mice also exhibited improved discrimination between a previously encountered odor stimulus (soiled bedding of gender- and strain-matched juvenile mice) and two subsequent unfamiliar odor stimuli at 1 hr and 24 hrs later as compared to non-enriched AY mice (both P< .05; ANOVA).Conclusions: Environmental enrichment appears to reverse the behavioral impairment induced by AY-9944 treatment during postnatal development. Further studies are required to determine the effect of environmental enrichment in seizure severity and in the GABAB receptor modulation in the chronic model of atypical absence seizures.