Using rodents to model schizophrenia and substance use comorbidity

• Rodents are suited for the study of schizophrenia and substance use disorder comorbidity.
• Specific nicotinic receptors help explain high rates of smoking in schizophrenics.
• Drug self-administration and sensitization are enhanced in a developmental model.
• Models of rare and common gene variants show dual diagnosis phenotypes.
• Genetic models given chronic cannabis test the two-hit hypothesis of dual diagnosis.

Schizophrenia and substance use disorders (SUD) often occur together, yet it is unclear why this is the case or how best to manage dual diagnosis. Rodent models are well suited to study how genes and environment interact to impact neurodevelopment, brain function and behaviors relevant to dual diagnosis. Indeed a variety of rodent models for schizophrenia display behavioral and physiological features relevant to SUD including: neurodevelopmental models, models of a rare variant (Disc1), to models of common variants (neurexin, dysbindin and neuregulin), and models of various gene-drug interactions. Thus it may be worthwhile to probe models of schizophrenia for insights relevant to SUD and dual diagnosis. However, future studies on dual diagnosis should involve characterization beyond measuring locomotor responses to self-administration tasks, include drug classes other than psychostimulants, and dissect the neuroadaptations that underlie risk for dual diagnosis.