Ingestion of
ethanol during pregnancy can result in teratogenic effects in humans, including significant and long-lasting neurobehavioral deficits. Similar results are seen in guinea pigs with chronic prenatal
ethanol exposure (CPEE) via maternal
ethanol administration, which produces deficits in Morris water-maze performance and impaired hippocampal functioning (e.g., decreased long-term potentiation, LTP). In this study, we tested whether postnatal treatment with
fluoxetine, a
selective serotonin reuptake inhibitor, decreases some of the neurobehavioral impairments produced by CPEE. Timed, pregnant guinea pigs received
oral administration of
ethanol (4g/kg maternal
body weight) or isocaloric
sucrose pair feeding (control) for 5 days/week throughout gestation. Offspring of the CPEE and control groups were randomly assigned to receive either
fluoxetine (10mg/kg
body weight/day) or saline intraperitoneally from postnatal day 10 to 48. Subsequent behavioral tests in the Morris water-maze revealed a significant increase in thigmotaxic swimming in CPEE offspring without apparent signs of impairment in spatial mapping of the hidden escape platform. Measures of hippocampal short- and long-term plasticity (paired-pulse facilitation, frequency facilitation, and LTP) were unaffected by CPEE, consistent with the behavioral data indicating normal hippocampal functioning. Postnatal
fluoxetine administration resulted in a significant loss of
body weight, but did not affect the increased thigmotaxic swimming following CPEE. These results indicate that changes in search strategies in the water-maze might be a highly sensitive index of CPEE-induced neurobehavioral toxicity that can occur in the absence of significant hippocampal dysfunction. Further, these data demonstrate that
fluoxetine, at the selected treatment regime, does not mitigate the thigmotaxic swimming response to CPEE in the guinea pig.