Sex Differences in Psychosis: Focus on Animal Models

Methamphetamine-induced locomotor sensitization in mice is not associated with deficits in a range of cognitive, affective and social behaviours: interaction with brain-derived neurotrophic factor Val66Met genotype

“…Several mouse and rat models of schizophrenia show profound differences between males and females (van den Buuse 2010; Gogos and van den Buuse 2022), consistent with sex differences in symptom profile and epidemiology in schizophrenia Gogos and van den Buuse 2022). Importantly, there are also sex differences in the pharmacokinetics and metabolism of Meth, which could lead to differential effects on behaviour (Gogos and van den Buuse 2022;Jaehne et al, 2022). The slightly higher effect of acute Meth on locomotor activity in female mice compared with male mice is consistent with such differences (Fig.…”

“…The specific effect of prior Meth treatment on spontaneous exploratory locomotor hyperactivity seen only in female mice was not mirrored by sex differences in the effect of Meth on other behaviours. Several mouse and rat models of schizophrenia show profound differences between males and females (van den Buuse 2010; Gogos and van den Buuse 2022), consistent with sex differences in symptom profile and epidemiology in schizophrenia Gogos and van den Buuse 2022). Importantly, there are also sex differences in the pharmacokinetics and metabolism of Meth, which could lead to differential effects on behaviour (Gogos and van den Buuse 2022;Jaehne et al, 2022).…”

The Impact of Muscarinic Antagonism on Psychosis-Relevant Behaviors and Striatal [11C] Raclopride Binding in Tau Mouse Models of Alzheimer’s Disease

“…Tau pathology accrues at different rates and begins at different ages in P301L-based and htau models (htau later), and the behavioral experiments were designed to take place after pathology begins to develop but significantly prior to the onset of any motor impairments from posterior and spinal tau pathology that could impact locomotor assessments [ 59 , 61 ]. We utilized female mice for comparisons, as tau transgenic expression is sex dependent, with females exhibiting more aggressive pathology [ 62 ], and as drug-induced changes in locomotion and sensorimotor gating have been shown to be sex-dependent [ 14 ].…”

“…An obstacle to drug development in AD psychosis has been the lack of appropriate preclinical models to test novel therapies [ 12 ]. Drug development pipelines for clinical trials in AD utilize transgenic neuropathologic animal models, targeting cognitive phenotypes to test their compounds, before going into humans [ 13 ], while antipsychotic agents are developed by targeting relevant behavioral phenotypes in the models: locomotor hyperactivity (often drug-induced) and sensorimotor gating [ 12 , 14 , 15 , 16 ]. Sensorimotor gating is an involuntary faculty that reflects the capacity to attend to an ongoing sensory stimulus and gate the motor response to a subsequent distracting startle stimulus; prepulse inhibition (PPI) of the acoustic startle reflex—the dampening of an automatic startle-induced contracture of skeletal muscle that represents a defensive posture [ 17 ] with an ongoing (prepulse) stimulus—is an experimental model used for the quantification of sensorimotor gating [ 18 ].…”

Interaction of Brain-Derived Neurotrophic Factor with the Effects of Chronic Methamphetamine on Prepulse Inhibition in Mice Is Independent of Dopamine D3 Receptors

“…This allowed us to study the effect of BDNF deficiency on its own or in the presence of additional deletion of D3 receptors, as well as the effect of D3 receptor deletion on its own or in the presence of BDNF deficiency. Because several previous studies have shown profound sex differences in psychosis-like behaviour [ 38 , 39 ], we used both male and female mice.…”