P2X receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in the piriform cortex.

P2X receptors are implicated in the pathophysiology of psychiatric conditions such as depression and bipolar disorder. P2X receptors regulate the release of pro-inflammatory cytokines from microglia, and gain-of-function P2X mutations may contribute to the neuroinflammation found in affective disorders. However, the role of this receptor in mediating other mental health conditions and aberrant behaviours requires further examination.

The Differential Binding of Antipsychotic Drugs to the ABC Transporter P-Glycoprotein Predicts Cannabinoid-Antipsychotic Drug Interactions.

Cannabis use increases rates of psychotic relapse and treatment failure in schizophrenia patients. Clinical studies suggest that cannabis use reduces the efficacy of antipsychotic drugs, but there has been no direct demonstration of this in a controlled study. The present study demonstrates that exposure to the principal phytocannabinoid, Δ-tetrahydrocannabinol (THC), reverses the neurobehavioral effects of the antipsychotic drug risperidone in mice.

The first CNS-active carborane: A novel P2X7 receptor antagonist with antidepressant activity.

Relative to other polycyclic frameworks (1-3), a carborane cage (4 and Cs·5) exerts a significant biological effect as an inhibitor of the purinergic P2X7 receptor (P2X7R) which allows one to target depression in vivo and thus demonstrate, for the first time, that a carborane has the capacity to modify CNS activity.

Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice.

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype.

Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice.

Neuregulin 1 (NRG1) is linked to an increased risk of developing schizophrenia and cannabis dependence. Mice that are hypomorphic for Nrg1 (Nrg1 HET mice) display schizophrenia-relevant behavioral phenotypes and aberrant expression of serotonin and glutamate receptors. Nrg1 HET mice also display idiosyncratic responses to the main psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol (THC).

Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine.

Methamphetamine use triggers psychosis in genetically vulnerable individuals, however the exact nature of this genetic predisposition requires elucidation. In addition, adolescence may be a particular period of neurodevelopmental vulnerability to the actions of methamphetamine; interestingly, this period coincides with a higher likelihood of onset of schizophrenia and drug experimentation. In the current study we investigated whether adolescent mice heterozygous for the schizophrenia susceptibility gene neuregulin 1 (Nrg1 HET mice) exhibit altered behavioural responses to methamphetamine (0.

Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9)-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice.

The 2nd Schizophrenia International Research Society Conference, 10-14 April 2010, Florence, Italy: summaries of oral sessions.

The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews.

Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects.

The schizophrenia susceptibility gene neuregulin 1 modulates tolerance to the effects of cannabinoids.

Cannabis increases the risk of schizophrenia in genetically vulnerable individuals. In this study we aim to show that the schizophrenia susceptibility gene neuregulin 1 (Nrg1) modulates the development of tolerance to cannabinoids in mice. Nrg1 heterozygous (HET) and wild-type (WT) mice were treated daily for 15 d with the synthetic analogue of Δ9-tetrahydrocannabinol, CP55,940 (0.

Chronic treatment with Delta(9)-tetrahydrocannabinol impairs spatial memory and reduces zif268 expression in the mouse forebrain.

Few studies have investigated the effects of chronic cannabinoid exposure on memory performance and whether tolerance occurs to cannabinoid-induced memory impairment. Here, we studied the effects of repeated exposure to Delta-tetrahydrocannabinol (THC: 1 mg/kg) on spatial memory and zif268 expression in mice. One group of animals was not pretreated with THC, whereas another group was injected with 13 daily injections of THC before memory testing in the Morris water maze.