Schizophrenia is a chronic debilitating neuropsychiatric disorder affecting approximately 1% of the population worldwide. Research into the psychotic disorder of schizophrenia, involves multiple animal models as a tool, including in the pre-clinical development of drugs. Particularly, Creative Biolabs provides an amphetamine-induced “positive” schizophrenia model to assess the efficacy of novel antipsychotic drugs.
Introduction of Amphetamine Model of Schizophrenia
As dopamine dysregulation with hyperfunction of the mesolimbic dopamine system was the original tenet theory underlying the basis of schizophrenia, the first animal models were developed on the basis of pharmacological manipulation to attempt to mimic this feature. Early efforts at modeling schizophrenia in animals relied on the acute administration of indirect dopamine agonists such as amphetamine or direct dopamine receptor agonists such as apomorphine to induce a transient central hyperdopaminergia. Typically, a single administration of 0.5-1.0 mg/kg of amphetamine is used to produce hyperlocomotion in rats, where higher doses (2.0-5.0 mg/kg) induce stereotypy and deficits in latent inhibition and pre-pulse inhibition (PPI). However, acute administration of amphetamine in animals does not consistently produce impairments in their performance on cognitive tasks that are considered analogs of those that people with schizophrenia perform poorly on. Similarly, impairments in social interaction or other behaviors relevant to negative symptoms are not induced by acute administration of pro-dopamine drugs.
Fig.1 Dopamine pathways and associated brain regions. VTA, ventral tegmental area. (Jones et al. 2011)
Because a single administration of amphetamine produces only a short-lived hyperdopaminergia and related behavioral effects, many investigators have attempted to model psychosis in animals using chronic administration of amphetamine, which induces a persistent sensitization and more robustly models symptoms than a single injection. Sensitized animals display persistent deficits in some cognitive tasks relevant to schizophrenia, whereas others are not affected such as deficits in social interaction and behaviors that are reminiscent of the negative symptoms of schizophrenia. Biochemical and structural changes are induced in the brain by chronic administration of amphetamine in animals, which may account for the persistent changes observed in behavioral and cognitive measures.
Features of Amphetamine Model of Schizophrenia
Assessments
Creative Biolabs conducts assessments including but not limited to:
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