Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons.

Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Here we report on the behavioral effects of psychostimulants in DAT-Cnr2 conditional knockout (cKO) mice with selective deletion of type 2 cannabinoid receptors in dopamine neurons.

Behavioral Evaluation of Seeking and Preference of Alcohol in Mice Subjected to Stress.

The alcohol preference model is one of the most widely used animal models relevant to alcoholism. Stressors increase alcohol consumption. Here we present a protocol for a rapid and useful tool to test alcohol preference and stress-induced alcohol consumption in mice.

Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin.

Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.

Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.

Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice.

Dietary docosahexaenoic acid alleviates autistic-like behaviors resulting from maternal immune activation in mice.

The prevalence of autism spectrum disorders over the last several decades has risen at an alarming rate. Factors such as broadened clinical definitions and increased parental age only partially account for this precipitous increase, suggesting that recent changes in environmental factors may also be responsible. One such factor could be the dramatic decrease in consumption of anti-inflammatory dietary omega-3 (n-3) polyunsaturated fatty acids (PUFAs) relative to the amount of pro-inflammatory omega-6 (n-6) PUFAs and saturated fats in the Western diet.

Psychiatric disturbances regulate the innate immune system in CSF of conscious mice.

Environment may affect brain activity through cerebrospinal fluid (CSF) only if there are regulatory molecules or cascades in CSF that are sensitive to external stimuli. This study was designed to identify regulatory activity present in CSF, better elucidating environmental regulation of brain function. By using cannulation-based sequential CSF sampling coupled with mass spectrometry-based identification and quantification of proteins, we show that the naive mouse CSF harbors, among 22 other pathways, the innate immune system as a main pathway, which was downregulated and upregulated, respectively, by acute stressor (AS) and acute cocaine (AC) administrations.

Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders.

Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1).

A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands.

Marijuana use activates cannabinoid receptors (CB-Rs) producing several behavioral effects related to addiction, mood, and appetite. We investigated the association between CNR2 gene, which encodes cannabinoid CB2 receptor (CB2-R) and eating disorders in 204 subjects with eating disorders and 1876 healthy volunteers in Japanese population. The effect of treatment with CB2-R ligands on mouse food consumption was also determined.

Behavioral effects of CB2 cannabinoid receptor activation and its influence on food and alcohol consumption.

Consumers of marijuana typically feel a strong, compulsive desire to consume food. Although past research revealed that the CB1 cannabinoid receptor is a potent regulator of food intake, the functional presence of neuronal CB2 cannabinoid receptors in the brain has been controversial. The role of CB2 receptors in food and alcohol consumption and the behavioral effects of CB2 receptor ligands are not well characterized.

Exaggerated responses to stress in the BTBR T+tf/J mouse: an unusual behavioral phenotype.

This study shows that the BTBR T+tf/J mouse, a model for autism spectrum disorder (ASD), has increased levels of the stress hormone corticosterone, when compared to C57BL/6J mice. In addition, we have shown that tail suspension of the BTBR produces a heightened anxiety response in the elevated plus maze. These results suggest that the BTBR mouse is stressor-reactive exhibiting hormone responses that might predispose it to ASD.

Genetic and developmental influences on infant mouse ultrasonic calling. III. Patterns of inheritance in the calls of mice 3-9 days of age.

Infant mice produce ultrasonic calls that may elicit retrieval by adult mice. Age-related differences and genetic effects, such as additivity and directional dominance, have been found for most call characteristics at 3 days of age. Significant maternal effects have been reported for calling rate.

The effects of cold, rotation, and genotype on the production of ultrasonic calls in infant mice.

There has been a revival of interest recently in the ultrasonic calls of infant rodents as investigators are using them to assess neurobehavioral development and animal models of anxiety. We compared the rates of ultrasonic calling of infant mice of two genotypes in two situations, cold and rotation. The subjects of study were 169 mouse pups from 29 litters and of two F1 genotypes, C57BL/10J x DBA/2J and C57BL/10J x SJL/J.

Prenatal cocaine exposure alters maternal retrieval behavior in mice.

Previous studies have demonstrated alterations in maternal retrieval behavior as a result of direct cocaine exposure. To establish the influence of prenatal cocaine exposure on pup retrieval, we exposed pups of three F1 genotypes by injecting their mothers (all C57BL/10J strain) with 20 mg/kg cocaine hydrochloride or saline subcutaneously on gestation days 7 to 17. When those pups became adults, control and exposed females were mated with males of the same genotype and tested for pup retrieval on postpartum days 4 and 5.

Nitric oxide in CsA-induced hypertension: role of beta-adrenoceptor antagonist and thromboxane A2.

Cyclosporine A (CsA) is an immunosuppressive agent, which also causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for 7 days.

The effects of prenatal cocaine exposure and genotype on the ultrasonic calls of infant mice.

Estimates are that as many as 44,000 humans are exposed to cocaine in utero per year. In this study we examined the effects of prenatal cocaine exposure on one aspect of the mother-infant relationship in mice, infant ultrasonic calls. We mated C57BL/10J female mice with males of three different inbred strains (producing pups of three different F(1) genotypes).

Genetic and developmental influences on infant mouse ultrasonic calling. II. Developmental patterns in the calls of mice 2-12 days of age.

Infant house mice, Mus musculus, produce ultrasonic calls that reliably lead to retrieval by adult mice. While individual differences in calls have been demonstrated both among and within species, the influences of age and sex on call characteristics have not been systematically investigated in mice. This study examined the influences of age, sex, and genotype (inbred versus hybrid) on the rate, length, and frequency characteristics of the calls of 486 male and female mice from 2 to 12 days of age.

Genetic and developmental influences on infant mouse ultrasonic calling. I. A diallel analysis of the calls of 3-day olds.

Ultrasonic calls produced by young mice reliably elicit investigation and retrieval by adults. While there are large individual differences in the characteristics of these calls, little work has been done to partition that variation. We completed a 4 x 4 diallel cross and Hayman analyses on several characteristics of these cries.

Issues in the genetics of social behavior: revisited.

Though social behavior has not been overlooked by behavior geneticists, the number of studies is small when compared to those on individual traits. One reason for the neglect may be the difficulty of making connections between genes and social behaviors, which by definition involve the interaction of two or more organisms. Fuller and Hahn (1976) addressed this issue and described three means of establishing social groups that would facilitate genetic analysis.