While the positive symptoms of schizophrenia such as disorganized speech, delusions, and hallucinations are unique to humans, in recent years there has been remarkable progress in modeling positive-like symptoms in rodents using pharmacological probes accompanied by relevant behavioral paradigms such as drug-induced hyperlocomotion, drug-induced stereotypy and pre-pulse inhibition (PPI) of the acoustic startle response. Locomotor behavior, stereotypy and PPI often display differential sensitivity to psychotomimetic drugs that possess slightly different mechanisms of action. Non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as the recreational drug phencyclidine (PCP), the dissociative anesthetic (and rapid-acting antidepressant) ketamine and the potent highly-selective antagonist dizocilpine (MK-801) lead to secondary dopaminergic dysregulation; normally, descending corticobrainstem glutamate tonically inhibit the mesolimbic dopaminergic pathway through inhibitory interneurons. When NMDARs are hypofunctional, a disinhibited and hyperactive mesolimbic pathway could result in psychosis, while in the cortex a hypodopaminergic state may evolve. Hypofunction of NMDARs could thus represent a convergence point for progression and insistence of positive symptoms of schizophrenia.

We offer several acute pharmacological models of psychosis based on the agent administered and behavioral outcome measured. These models include:

MK-801 -induced hyperlocomotion
MK-801 -induced PPI deficits
Ketamine -induced hyperlocomotion
Ketamine -induced stereotypic behavior

References:

van den Buuse M. Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull. 2010.