Sue J Cho1, David M Lovinger2, Prosper N'Gouemo1. 1. Department of Pediatrics, Georgetown University Medical Center, Washington, DC, USA. 2. Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.
Abstract
AIMS: Prenatal alcohol exposure (PAE) is associated with a higher likelihood of developing generalized tonic-clonic seizures (GTCS) in infants and children. However, experimental studies of PAE-related seizures have yielded conflicting results. Here, we investigated the effect of acute PAE on N-methyl-D-aspartate (NMDA)-induced seizures in developing rats. METHODS: Pregnant Sprague Dawley rats were given an oral dose of either ethanol (5 g/kg body weight) or vehicle on embryonic day 18. The offspring were tested for susceptibility to NMDA-induced seizures on postnatal day 7 (P7), 21 (P21), 35 (P35), and 42 (P42). Specifically, the prevalence and latency of NMDA-induced continuous wild running-like behaviors (CWR), flexion seizures (FS), wild running seizures (WRS), GTCS, and tonic seizures (TS) were recorded and analyzed. RESULTS: N-methyl-D-aspartate-induced seizures consisted of CWR, FS, GTCS, and TS in <P21 rats, while WRS, GTCS, and TS were observed in >P21 rats. Thus, GTCS were consistently observed during development. PAE significantly increases the prevalence of GTCS in female and male P7-P21 rats and P7-P35 rats, respectively, but not in older rats. PAE also increases the prevalence of TS in male, but not female P21-P35 rats. CONCLUSIONS: The PAE animal model of GTCS may provide a new opportunity to investigate the mechanisms that underlie neuronal hyperexcitability in developing animals prenatally-exposed to alcohol.
AIMS: Prenatal alcohol exposure (PAE) is associated with a higher likelihood of developing generalized tonic-clonic seizures (GTCS) in infants and children. However, experimental studies of PAE-related seizures have yielded conflicting results. Here, we investigated the effect of acute PAE on N-methyl-D-aspartate (NMDA)-induced seizures in developing rats. METHODS: Pregnant Sprague Dawley rats were given an oral dose of either ethanol (5 g/kg body weight) or vehicle on embryonic day 18. The offspring were tested for susceptibility to NMDA-induced seizures on postnatal day 7 (P7), 21 (P21), 35 (P35), and 42 (P42). Specifically, the prevalence and latency of NMDA-induced continuous wild running-like behaviors (CWR), flexion seizures (FS), wild running seizures (WRS), GTCS, and tonic seizures (TS) were recorded and analyzed. RESULTS:N-methyl-D-aspartate-induced seizures consisted of CWR, FS, GTCS, and TS in <P21rats, while WRS, GTCS, and TS were observed in >P21rats. Thus, GTCS were consistently observed during development. PAE significantly increases the prevalence of GTCS in female and male P7-P21rats and P7-P35rats, respectively, but not in older rats. PAE also increases the prevalence of TS in male, but not female P21-P35rats. CONCLUSIONS: The PAE animal model of GTCS may provide a new opportunity to investigate the mechanisms that underlie neuronal hyperexcitability in developing animals prenatally-exposed to alcohol.
Authors: C Ikonomidou; P Bittigau; M J Ishimaru; D F Wozniak; C Koch; K Genz; M T Price; V Stefovska; F Hörster; T Tenkova; K Dikranian; J W Olney Journal: Science Date: 2000-02-11 Impact factor: 47.728