Abstract no.: 7 Effects of gestational day 11 exposure to methylazoxymethanol acetate on Morris water maze performance, prepulse inhibition and latent inhibition in adult male Wistar rats

Abstract

In the present study, gestating dams were treated with methylazoxymethanol acetate (MAM). MAM causes DNA damage, and this mechanism kills actively dividing neurons and thereby disrupts neurogenesis. This has been considered to be a neurodevelopmental animal model of schizophrenia (Talamini et al. 1998, Brain Res. 789:293–306). Schizophrenic patients show deficits in learning/memory function, sensorimotor gating and latent inhibition. Our aim was to investigate whether we could observe similar deficits in adult offspring of MAM‐treated dams.Methods: Pregnant Wistar rats received an injection of either solvent or 20 mg/kg (IP) of MAM on the 11th day of gestation. 12 hours later, the rats received a second injection with either saline or MAM. Four groups of animals were tested at adult age (>75 days old): (1) offspring of untreated naïve mothers; (2) offspring of mothers that received two solvent injections (sol/sol); (3) offspring of mothers that first received MAM and solvent with the second injection (MAM/sol); (4) offspring of mothers subjected to two MAM injections (MAM/MAM). The Morris water maze test was used as a measure for spatial learning and mnemonic capabilities. Sensorimotor gating was studied by means of the prepulse inhibition (PPI) paradigm. Finally, the latent inhibition (conditioned taste aversion) paradigm was used to assess learned irrelevance.Results: (1) Animals learned to find the invisible platform in the Morris water maze. MAM did not disrupt acquisition in this test. There were also no differences in long‐term spatial memory in the Morris water maze probe trial. (2) Treatment groups did not differ in the level of PPI or startle reactivity. (3) No effects of MAM treatment were found on latent inhibition. (4) However, there was a difference in body weight between treatment groups: MAM/sol animals had a lower body weight than animals from the naïve group and MAM/MAM rats were significantly lower in weight compared to both the naïve and sol/sol animals.Conclusion: Gestational day 11 exposure to MAM did not disrupt learning/memory function, prepulse inhibition or latent inhibition in adult male Wistar rats. The lack of effects of MAM on the above mentioned behavioral parameters in the present study brings into question the relevance of this model for the cognitive and information processing aspects of schizophrenia.