Methylazoxymethanol acetate

MAM animal models

Schizophrenia

In rat models, the specific effect of MAM on neural development depends on the gestational age of the subject. At the seventeenth gestational day (GD17), administration of MAM produces behavioral and histopathological patterns found in schizophrenia. Methylazoxymethanol acetate administered at GD17 reduces the thickness of the hippocampus and the thalamus. The locomotor effects of amphetamines and the spontaneous firing rate of dopaminergic neurons in the ventral tegmental area are increased. In alternating maze tests, GD17 MAM rats quickly learned the first rule, but took longer to accommodate to alterations to the rule; this is thought to indicate deficits in working spatial memory, which is also impaired in schizophrenia.

Epilepsy

Exposure to MAM before birth increases susceptibility to epileptic seizures caused by flurothyl. In some epilepsy rat models, MAM is administered at the fifteenth gestational day. Previous studies have found impaired cognitive function in GD15 MAM rats, and a reduced seizure threshold. At the cellular level, dysplastic hippocampal neurons in the MAM model were shown to have reduced potassium current function and expression for the Kv4.2 channel subunit These findings may contribute to the spontaneous seizures and reduced seizure thresholds seen in this model.

References

References

1. "Methylazoxymethanol Acetate – Compound Summary". [[National Center for Biotechnology Information]].
2. Jones, CA. (1 October 2011). "Animal models of schizophrenia". [[British Journal of Pharmacology]].
3. Baraban, Scott C.. (31 March 1996). "Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment". Epilepsy Research.
4. Hradetzky, Eva. (28 September 2011). "The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus". Neuropsychopharmacology.
5. Harrington, Emily. (January 2007). "Altered glutamate receptor-transporter and spontaneous seizures in rats exposed to methylazoxymethanol in utero". Epilepsia.
6. Moshé, editors, Asla Pitkänen, Philip A. Schwartzkroin, Solomon L.. (2006). "Models of seizures and epilepsy". Elsevier Academic.
7. Castro, Peter. (1 September 2001). "AHippocampal heterotopia lack functional Kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy.". Journal of Neuroscience.