Animal Models of Psychosis: Current State and Future Directions

Abstract

Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability.

Chronic clozapine treatment restrains via HDAC2 the performance of mGlu2 receptor agonism in a rodent model of antipsychotic activity

“…In line with previous studies [13,15,16,18], we showed that the mGlu2 receptor is necessary to prevent via administration of the orthosteric mGlu2/3 receptor agonist LY379268 the effects of MK801-induced locomotor activity. Stereotypy is characterized by repetitive behavior and has been noted in patients with psychosis and also in several pharmacological human and rodent models of psychosis [44,45]. Our data further extend the involvement of mGlu2 on the antipscyhotic phenotype of mGlu2/3 agonists by showing that mGlu2 receptor is, at least in part, necessary for the effects of LY379268 on the stereotyped behavior induced by MK801.…”

“…Coadministration of LY379269 along with MK801 limited locomotor activity to the periphery of the corners of the test chamber ( Supplementary Fig 1c). Nevertheless, considering that dissociative drugs also affect the level of stereotyped and repetitive behaviors, such as repetitive licking, chewing and grooming, in rodents [44,45], these findings raise the question of whether mGlu2/3 receptor agonists affect the MK801-induced hyperlocomotor activity component alone, or together with stereotyped behavior.…”

Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype

“…Notably, memory impairment is unlikely to underlie these locomotor changes, since we show intact memory performance in the NOR task during METH abstinence. Increased psychostimulant-induced repetitive stereotypic/rearing behavior has been previously associated with psychotic properties of drugs of abuse (Reeves et al, 2003) and general psychotic symptoms in animals (see Forrest et al, 2014). Additionally, disruptions of pre-pulse inhibition were reported in mice following a similar administration/withdrawal paradigm used in the present study (7-day METH (1 mg/kg) administration and 7-day withdrawal; (Arai et al, 2008)).…”

Melatonin recovers sleep phase delayed by MK‐801 through the melatonin MT2 receptor‐ Ca2+‐CaMKII‐CREB pathway in the ventrolateral preoptic nucleus

“…47 Indeed, NMDAR hypofunction following the administration of MK-801 is one of strategies used to model in some rodents but not all of the symptoms of human psychosis including stereotypy and hyperactivity. 48,49 In conclusion, our data demonstrate that MLT can improve NMDAR-mediated sleep impairments by acting on the homeostatic sleep center VLPO through a mechanism involving the MLT MT 2 receptor-Ca 2+ -CaMKII-CREB pathway. These findings add novel knowledge on the neurobiological mechanism through which MLT can regulate the sleep-wake cycle, and suggest that the MLT system may be a good target for the treatment of sleep impairments in psychiatric disorders associated with NMDAR dysfunction.…”