Sex-specific transgenerational effects of morphine exposure on reward and affective behaviors.

Current estimates indicate that millions of people in the United States abuse opioid drugs, which may also affect their offspring. To determine whether parental exposure to morphine alters reward and affective behaviors in subsequent generations we exposed male and female C57BL/6NTac mice to morphine (75 mg) or placebo pellets for 4 weeks. Naïve mice were used as mating partners to create subsequent generations (F1 and F2).

Effects of nicotine and stress exposure across generations in C57BL/6 mice.

Chronic administration of nicotine or exposure to stress can produce long-lasting behavioral and physiological changes in humans and animals alike. Further, the impact of nicotine and stress exposure can be inherited by offspring to produce persistent changes in physiology and behavior. To determine if nicotine and stress interact across generations to influence offspring behavior we exposed F0 male mice to nicotine and F1 male and female mice to chronic unpredictable stress during adolescence.

Dietary challenges differentially affect activity and sleep/wake behavior in mus musculus: Isolating independent associations with diet/energy balance and body weight.

Background And Aims: Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities. Here, we use dietary challenges to parse apart the relative influence of diet and/or energy balance from body weight on various metabolic and behavioral outcomes.

Adolescent Chronic Unpredictable Stress Exposure Is a Sensitive Window for Long-Term Changes in Adult Behavior in Mice.

Adolescence is a time period in development when the brain undergoes substantial remodeling in response to the environment. To determine whether a stressful experience during adolescence affects adult behavior, we exposed adolescent male and female C57BL/6J mice to chronic unpredictable stress (CUS) for 12 days starting at postnatal day 28 (PND28). We also exposed adult male and female mice to CUS for 12 days beginning at PND70 to determine whether adolescence is a sensitive time period when stress can have long-lasting effects on behavior.

Long-lasting effects of adolescent oxycodone exposure on reward-related behavior and gene expression in mice.

Rationale: Prescription opioid abuse and transition to heroin use are growing problems in the USA. However, the long-term consequences of adolescent prescription opioid abuse on subsequent drug use and affective-like behavior are unknown.

Objectives: This study aims to determine if adolescent exposure to oxycodone alters the rewarding effects of morphine, anxiety-like behavior, and reward-related gene expression later in adulthood.

Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine.

Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations.

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

Although nicotine mediates its effects through several nicotinic acetylcholine receptor (nAChR) subtypes, it remains to be determined which nAChR subtypes directly mediate heightened anxiety during withdrawal. Relative success in abstinence has been found with the nAChR partial agonist varenicline (Chantix; Pfizer, Groton, CT); however, treatment with this drug fails to alleviate anxiety in individuals during nicotine withdrawal. Therefore, it is hypothesized that success can be found by the repurposing of other nAChR partial agonists for cessation therapies that target anxiety.

Phosphatidylinositol 3'-kinase, mTOR, and glycogen synthase kinase-3β mediated regulation of p21 in human urothelial carcinoma cells.

Background: The PTEN/Phosphatidylinositol 3'-kinase (PI3-kinase) growth factor signaling pathway plays a critical role in epithelial tumor development in a multitude of tissue types. Deletion of the Pten tumor suppressor gene in murine urothelial cells in vivo results in upregulation of cyclin-dependent kinase inhibitor p21. We have previously shown in mice that p21 expression blocks an increase in urothelial cell proliferation due to Pten deletion.