Animal Models of Schizophrenia

The two articles this week each proposed their own animal model for schizophrenia. Kellendonk et al. (2006) discussed a model that overexpressed D2 receptors in the striatum, while Moore et al. (2006) used a model that exposed rats to methylazoxymethanol acetate (MAM) on embryonic day 17. Each of these articles looked at changes in the brain, along with a few key behavioral changes that are also associated with schizophrenia.

Personally, I thought that Moore et al. (2006) did a better job representing schizophrenia throughout the brain. The MAM-E17 model led to many structural findings that are consistent with the neuropathological and imaging findings of human schizophrenia studies (reduced cortical thickness, hippocampal volume correlates with PFC thickness, reduced size of medial dorsal thalamus, etc.). Additionally, this model showed that some of the changes in the dopamine system do not occur until after puberty, which is consistent with schizophrenia (which usually has an onset in early-mid twenties in men and mid-late twenties in women). Kellendonk et al. (2006) focused solely on changes related to D2 receptors in the striatum, and I think that it is clear that there are many other changes in the brains of patients with schizophrenia that aren’t directly related to D2 receptor overexpression. However, I do think that D2 receptor expression is extremely important in schizophrenia, and I think that Kellendonk et al. (2006) did a good job at showing how this overexpression effects the PFC and some key behavioral components of schizophrenia.

Though I found the Moore et al. (2006) model to be a little bit more inclusive of the vast array of brain changes seen in schizophrenia, I had issues with both models. I know that in animal models, we cannot see all of the same things as with human models. However, many really important aspects of schizophrenia were not evident in either model. First of all, positive symptoms (which are such a hallmark sign of schizophrenia), like hallucinations, delusions, and any sort of responding to internal stimuli, are obviously not present in either of the models. I understand that this is nearly impossible to examine in rodent models, but since it is such a key component to the disease, I think that it is hard to say a treatment could have clinical implications if it is tested using an animal model that is still so behaviorally different from the human population. Additionally, even some of the negative signs of schizophrenia were not evident in either model (withdrawal, isolation, flat affect, catatonia). Another critique that I have about both of these models is that they do not take into account any environmental factors in the development of schizophrenia. Though schizophrenia is largely a brain disease, it is definitely influenced by things like family life, SES, life stressors, etc. Though I thought that Moore et al. (2006) did an especially good job at mimicking the brain changes in schizophrenia in a mouse model, I am still not necessarily convinced that this can truly be translated over into a human schizophrenia population.