Research Paper on Validity of the Schizophrenic Mouse for Preclinical Research

Validity of the Schizophrenic Mouse for Preclinical Research

Animal models that study the schizophrenic mouse for preclinical research include models of specific symptoms or signs and models of the full syndrome. Concerning clinical responsiveness and phenomena to antipsychotic drugs, models must be evaluated scientifically in terms of their predictive etiologic and construct validity.

The specification of the purpose for which the animal model has been designed is important in assessing and developing it, as the criteria that must be satisfied to establish its validity are determined by its intended purpose.

In the cross-species validity of the model, the confidence can be increased by focusing on particular symptoms or signs instead of syndromes.

Schizophrenic Mouse for Preclinical Research

For schizophrenia, one of the most difficult things to establish is the accuracy of the reproduction of the symptoms of a human condition by an animal model, which is also known as face validity.

Behavioral measures have been used extensively to establish the predictive and constructive validity of this schizophrenic mouse model. Some of the behavioral measures used are impaired attention, disruption of pre-pulse inhibition and horizontal locomotion.

In addition to this, to establish the validity of this model, some other measures used are molecular and cellular markers based on imaging studies and described changes in the human postmortem.

Changes in locomotor activity in mice have also been used to assess this model. From the psych stimulant model based on the dopamine hypothesis of schizophrenia, the original impetus for the use of locomotor activity measures has been derived.

To characterize the effects of both N-methyl-D-aspartate NMDA) and dopaminergic psych stimulants, the measures of locomotor hyperactivity were used extensively.

For the stereotyped behavior induced by amphetamine in humans, face validity was seen, as perseverative or stereotyped behaviors were stroked, and cross-species studies revealed locomotor hyperactivity.

Further, molecular and cellular markets were used to establish the validity of this model. In addition, functional findings from imaging studies performed on schizophrenia patients were also used.

In response to amphetamine in schizophrenia patients, an exaggerated dopamine release was demonstrated by these studies. Lastly, this model was validated based on its performance and whether a sound theoretical rationale was provided.


In models of psychiatric disorders, these characteristics, i.e., performance and providing a sound theoretical rationale, are called construct and predictive validity.

Latent inhibition (LI) and pre-pulse inhibition of startle (PPI) were other measures that were also considered, as they are reliable indicators of schizophrenia.

The disruptive effects of DA receptor agonists on PPI were also considered to depict the face validity of the model. Impaired in schizophrenia, a test of pre-attentional sensorimotor gating is referred to as PPI.

The stimulus-evoked changes in PPI in mice and humans are similar, and in both species, the PPI can be disrupted by the DA agonist Apo morphine.

Some degree of construct and predictive validity for this model was supported by an effect blocked by antipsychotics, i.e., the disruption in mice by PPI through the directive influence of DA into the nucleus acumens (NAC).

However, one of the limitations was the paucity of rigorous experimental data generated from clinical studies that established the predictive, etiologic, and construct validity of this schizophrenic mouse model.