Overview of Animal Models of Schizophrenia

Abstract

Animal models of schizophrenia may increase the understanding of the neurological abnormalities associated with the disorder and aid in the development of rational pharmacological treatments. Rather than attempting to model the entire syndrome of schizophrenia, a more biologically oriented approach to animal models has been to focus on specific symptoms of schizophrenia that are more objectively measured in the clinical population and more directly translatable to animals (e.g., observables or endophenotypes). This overview focuses on behavioral measures that have been investigated in rodent models of schizophrenia with varying degrees of predictive, etiological, and construct validity. Because of the severity of cognitive deficits in schizophrenia and their resistance to current treatments, there is a need to develop animal models specific to the cognitive symptoms of schizophrenia. In light of this need, this overview discusses rodent models of cognition with relevance to the core cognitive deficits observed in schizophrenia.

A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health

“…50 Disruption of sensorimotor gating by amphetamine is commonly used as a behavioural paradigm to model psychosis in rodents, and this effect can be blocked by antipsychotics. 72 Since Akt1 is inhibited following the stimulation of D2 receptors, the increased behavioural effect of amphetamine in Akt1 knockout mice supports the involvement of Akt inhibition in DArelated behavioural responses. However, DA regulates more than locomotion and sensorimotor gating.…”

Distinct cortical and striatal actions of a β-arrestin–biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties

“…AMPH-and PCP-induced hyperlocomotion are the two commonly used pharmacological models to test APD efficacy. Most APDs are D2R partial agonists or antagonists with varying potencies and efficacies (31,32,40,58) and inhibit either the AMPH-or PCP-induced locomotor response in mice (59). The AMPH-induced locomotor response is dependent on striatal DA release, whereas the behavioral effects of PCP are thought to be mediated by cortical disinhibition and activation of the corticostriatal pathway (48,50).…”

Interaction of genotype and environment: effect of strain and housing conditions on cognitive behavior in rodent models of schizophrenia

“…In order to bridge the translational gap, tests used in animal models have also been considered and selected for future use and development (Gilmour et al, 2012; Lustig et al, 2012). Domains such as verbal learning and memory cannot be translated to rodents, however processes such as attention, memory and executive control can be measured in a number of ways (Powell and Geyer, 2007) The tests selected for rodents that best reflect the cognitive constructs measured in patients include the five choice serial reaction time task (5C-SRTT) (Robbins, 2002) and sustained attention task (dSAT) for measuring attention (Lustig et al, 2012), the attentional set-shifting task (ASST) (Birrell and Brown, 2000) and reversal learning (Izquierdo and Jentsch, 2012) as measures of executive control and the radial arm maze (RAM) and delayed match to position (DMTP) task (Dudchenko, 2004), which provide the best assessment of working memory.…”