Injury-on-a-chip for modelling microvascular trauma-induced coagulation.

Blood coagulation is a highly regulated injury response that features polymerization of fibrin fibers to prevent the passage of blood from a damaged vascular endothelium. A growing body of research seeks to monitor coagulation in microfluidic systems but fails to capture coagulation as a response to disruption of the vascular endothelium. Here we present a device that allows compression injury of a defined segment of a microfluidic vascular endothelium and the assessment of coagulation at the injury site.

Paternal morphine alters offspring circulating beta-endorphin and corticosterone responses to oxycodone and cocaine.

Background: The opioid epidemic is leading to increased opioid use in adolescent populations. A growing body of evidence suggests that taking opioids during adolescence can disrupt normal development and impact future offspring. This study investigates the impact of paternal morphine exposure during adolescence on the hypothalamic-pituitary-adrenal (HPA) axis and release of endorphins in the offspring.

Neuroplasticity-related genes correlate with individual differences in distinct phases of oxycodone self-administration in male rats.

Opioid use disorder (OUD) is a chronic condition associated with long-lasting molecular and behavioral changes. Animals with prolonged access to opioids develop behaviors similar to human OUD. Identifying associated molecular changes can provide insight to underpinnings that lead to or maintain OUD.

Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.

Rationale: Transgenerational effects of preconception morphine exposure in female rats have been reported which suggest that epigenetic modifications triggered by female opioid exposure, even when that exposure ends several weeks prior to pregnancy, has significant ramifications for their future offspring.

Objective: The current study compares two mouse strains with well-established genetic variation in their response to mu opioid receptor agonists, C57BL/6J (BL6) and 129S1/svlmJ (129) to determine whether genetic background modifies the impact of preconception opioid exposure.

Methods: Adolescent females from both strains were injected daily with morphine for a total of 10 days using an increasing dosing regimen with controls receiving saline.

Effects of Maternal Separation on Effort-based Responding for Sucrose Are Associated with c-Fos Expression in the Nucleus Accumbens Core.

In both people and animals, exposure to adverse experiences early in life can alter neurodevelopment and lead to long-term behavioral effects, including effects on reward processing. In the current study, we use a well-validated rodent model of maternal neglect, maternal separation (MS), to investigate the impact of early life adversity on reward learning and motivation and identify associated modifications in cellular activation in reward-relevant areas. Litters of Long-Evans rats were separated from the dam for either 15 min (brief) or 180 min (prolonged)/day from postnatal day (PND)2 to PND14.

Intergenerational effects of preconception opioids on glucose homeostasis and hepatic transcription in adult male rats.

Adolescence represents a period of significant neurodevelopment during which adverse experiences can lead to prolonged effects on disease vulnerability, including effects that can impact future offspring. Adolescence is a common period for the initiation of drug use, including the use of opioids. Beyond effects on central reward, opioids also impact glucose metabolism, which can impact the risk of diabetes.

HPA axis dysfunction during morphine withdrawal in offspring of female rats exposed to opioids preconception.

Opioid use and abuse remain a significant public health problem, particularly in the United States. Indeed, it is estimated that up to 10% of youths (age 12-18) have taken opioids illicitly. A growing body of evidence suggests that this level of widespread opioid exposure can have effects that extend to subsequent generations.

Transgenerational effects on anxiety-like behavior following adolescent morphine exposure in female rats.

Global opioid use and misuse remains high, despite efforts to decrease rates of prescribing and diversion. Chronic exposure to opioids, particularly during critical periods of development, can lead to long-lasting effects, including effects that may extend to future generations. Using a rodent model, we have demonstrated significant transgenerational effects of female adolescent morphine exposure, despite the absence of in utero drug exposure.

Oxycodone Decreases Dendritic Complexity in Female but not Male Rat Striatal Neurons In Vitro.

The use of oxycodone in the past two decades has dramatically risen, yet the amount of research regarding how it impacts neuronal health is lacking. As prescription use and misuse in women of reproductive age increases there has been a corresponding increase in the number of infants who have been exposed to oxycodone in utero. Given the critical role of the striatum in motor control and reward regulation, the aim of the current study was to examine the effects of oxycodone on developing rat striatal neurons.

A history of opioid exposure in females increases the risk of metabolic disorders in their future male offspring.

Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation.

Paternal morphine exposure induces bidirectional effects on cocaine versus opioid self-administration.

The United States is in the midst of an opioid epidemic and is thus experiencing unprecedented levels of opioid exposure. A growing body of evidence has demonstrated that this may have consequences on multiple generations. The current set of experiments examined the effect of male adolescent opioid exposure on cocaine and opioid self-administration in the F1 generation.

Multi-, Inter-, and Transgenerational Effects of Drugs of Abuse on Behavior.

Transgenerational epigenetic inheritance is a burgeoning field that has recently garnered much attention. A growing body of evidence identifies behavioral phenotypes associated with inter-, multi-, and transgenerational studies following a wide variety of parental exposures. This chapter in current topics in behavioral neurogenomics examines the evidence for the presence of behavioral phenotypes and, in particular, the varied and often opposite behavioral responses observed with protocol shifts.

Challenges to the parental brain: Neuroethological and translational considerations.

Extending from research documenting adaptive parental responses in nonthreatening contexts, the influences of various neuroethological and physiological challenges on effective parenting responses are considered in the current review. In natural habitats, rodent family units are exposed to predators, compromised resources, and other environmental stressors that disrupt HPA axis functions. With the additional physiological demands associated with caring for offspring, alterations in stress-related neuroendocrine responsiveness contribute to adaptive responses in many challenging contexts.

Increased cocaine reward in offspring of females exposed to morphine during adolescence.

Rationale: A growing body of evidence demonstrates that environmental exposures can impact the physiology and behavior of subsequent generations. We have previously demonstrated reduced morphine self-administration in the F1 and F2 offspring of female rats exposed to morphine during adolescence.

Objectives: The current study was designed to determine whether attenuated self-administration for a substance not in the opioid class is also observed in the F1 progeny of adolescent morphine exposed females.

Oxycodone self-administration during pregnancy disrupts the maternal-infant dyad and decreases midbrain OPRM1 expression during early postnatal development in rats.

Opioid use and abuse has reached epidemic levels in the United States. As these drugs are frequently used by women of reproductive age, there has been a significant increase in the number of infants born to opioid dependent women. Few preclinical studies have examined voluntary opioid intake during pregnancy, and none have used intravenous self-administration.

Transgenerational blunting of morphine-induced corticosterone secretion is associated with dysregulated gene expression in male offspring.

A number of parental experiences, even when occurring prior to conception, have been shown to induce transgenerational effects beyond the first generation. In the case of exposure to drugs of abuse, studies in rodents suggest that offspring demonstrate significant differences in how they respond to the drug to which their parent was exposed. We have previously observed significant alterations in morphine analgesia, conditioned place preference and self-administration in the offspring of females exposed to morphine during adolescent development.

Modeling prenatal opioid exposure in animals: Current findings and future directions.

The past decade has seen a drastic rise in the number of infants exposed to opioids in utero. It is unclear what lasting effect this exposure may have on these children. Animal models of prenatal opioid exposure may provide insight into potential areas of vulnerability.

Transgenerational attenuation of opioid self-administration as a consequence of adolescent morphine exposure.

The United States is in the midst of an opiate epidemic, with abuse of prescription and illegal opioids increasing steadily over the past decade. While it is clear that there is a genetic component to opioid addiction, there is a significant portion of heritability that cannot be explained by genetics alone. The current study was designed to test the hypothesis that maternal exposure to opioids prior to pregnancy alters abuse liability in subsequent generations.

Adult Neurogenesis in the Female Mouse Hypothalamus: Estradiol and High-Fat Diet Alter the Generation of Newborn Neurons Expressing Estrogen Receptor α.

Estrogens and leptins act in the hypothalamus to maintain reproduction and energy homeostasis. Neurogenesis in the adult mammalian hypothalamus has been implicated in the regulation of energy homeostasis. Recently, high-fat diet (HFD) and estradiol (E2) have been shown to alter cell proliferation and the number of newborn leptin-responsive neurons in the hypothalamus of adult female mice.

Adolescent experience affects postnatal ultrasonic vocalizations and gene expression in future offspring.

The present study measured postnatal ultrasonic vocalization (USV) and gene expression to examine potential changes in communication and/or attachment in the offspring of mothers exposed to morphine during adolescence. Offspring of morphine-exposed (Mor-F1), saline-exposed (Sal-F1), or non-handled control (Con-F1) female Sprague-Dawley rats were tested for separation-induced distress calls and maternal potentiation of distress calls during early postnatal development. We also examined relative expression of dopamine D2 receptor and mu opioid receptor (oprm1) mRNA in the nucleus accumbens and hypothalamus in these offspring, as their activity has been implicated in the regulation of postnatal USV in response to maternal separation.

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.

Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring.