Modeling cholinergic aspects of schizophrenia: focus on the antimuscarinic syndrome

Symptoms of schizophrenia, commonly divided into positive symptoms, negative symptoms, and cognitive impairments, exhibit different sensitivity to pharmacological treatments. As such, they are typically modeled in animals by behavioral effects of drugs that evoke these symptoms in humans, such as amphetamine or phencyclidine (PCP). Despite the fact that muscarinic antagonists also evoke a schizophrenia-like syndrome ("antimuscarinic syndrome") and findings of cholinergic-related alterations in brains of schizophrenia patients, modeling schizophrenia using muscarinic manipulations has been infrequently considered, and the effects of muscarinic blockade on behavioral tasks relevant to schizophrenia have not been adequately characterized. The present review surveys recent attempts to model schizophrenia-related symptoms using manipulations causing cholinergic dysfunction, particularly muscarinic blockade, in well validated behavioral models of schizophrenia, such as prepulse inhibition and latent inhibition.