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Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia
Francois Gastambide1, Amy M Taylor2, Clare Palmer2
1Lilly Centre for Cognitive Neuroscience, Eli Lilly & Co. Ltd, Erl Wood Manor, Windlesham, UK. gastambidefr@lilly.com.
Abstract:
Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.
Insights
Methylazoxymethanol acetate (MAM) exposure in embryonic rats impairs spatial memory and reduces anxiety. These findings support MAM as a model for hippocampal dysfunction relevant to schizophrenia.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Behavioral Neuroscience
Background:
- Prenatal exposure to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) induces hippocampal pathology in adult rats.
- Existing literature shows discrepancies in the behavioral outcomes of this prenatal manipulation.
Purpose of the Study:
- To systematically assess the behavioral alterations induced by MAM E17 exposure using hippocampus-dependent tasks.
- To clarify the impact of MAM E17 on spatial memory, short-term memory, and anxiety levels.
Main Methods:
- Rats were exposed to MAM at E17, and behavioral assessments were conducted in adulthood.
- A battery of hippocampus-dependent tests was employed, including watermaze (hidden and visible platforms), Y-maze, spatial novelty preference, and elevated plus maze tasks.
- Control groups received saline injections.
Main Results:
- MAM E17-treated rats exhibited significant deficits in spatial reference memory in both aversive (watermaze) and appetitive (Y-maze) tasks.
- These spatial memory deficits were robust and replicated across multiple cohorts and laboratories.
- MAM-treated rats showed impairments in short-term memory (spatial novelty preference) and reduced anxiety (elevated plus maze).
- No significant effects were observed in non-spatial tasks (visible platform watermaze, visual discrimination).
Conclusions:
- MAM E17 administration leads to abnormal spatial information processing and reduced anxiety in rats.
- These behavioral changes parallel the effects of dorsal and ventral hippocampal lesions.
- The MAM E17 model effectively recapitulates aspects of hippocampal dysfunction relevant to schizophrenia.
