Enhanced heroin self-administration and distinct dopamine adaptations in female rats.

Increasing evidence suggests that females are more vulnerable to the harmful effects of drugs of abuse, including opioids. Additionally, rates of heroin-related deaths substantially increased in females from 1999 to 2017 [1], underscoring the need to evaluate sex differences in heroin vulnerability. Moreover, the neurobiological substrates underlying sexually dimorphic responding to heroin are not fully defined.

Acquisition of remifentanil self-administration: Enhanced in female rats but no effect of adolescent stress exposure.

Animal models of acquisition have been vital in shaping our understanding of vulnerability factors that influence susceptibility to drugs of abuse. Decades of research substantiates a number of biological, environmental, and behavioral factors that predict vulnerability - many of which have been important in the development of early intervention efforts in humans. The goal of the present study was to examine the acquisition of a synthetic opioid derivative in 66 adult male and female Long-Evans rats following histories of stress exposure during adolescence.

Behavioral economic demand as a unifying language for addiction science: Promoting collaboration and integration of animal and human models.

The intersection of pharmacological, psychological, and economic theory within behavioral economics has helped advance an understanding of substance use disorder. A notable contribution of this approach is the conceptualization of reinforcement from a behavioral economic demand perspective. Demand analyses provide a multidimensional view of reinforcement in which distinct behavioral mechanisms are measured that impact decision making and drug consumption.

Multiprobe Nuclear Imaging of the Cystic Fibrosis Lung as a Biomarker of Therapeutic Effect.

Nuclear imaging biomarkers illustrate unique aspects of lung physiology and are useful for assessing therapeutic effects in cystic fibrosis (CF) lung disease. We have developed a multiprobe method to simultaneously measure mucociliary clearance (MCC) and paracellular absorption (ABS). MCC is a direct measure of mucus clearance.

The influence of sex and estrous cyclicity on cocaine and remifentanil demand in rats.

The application of behavioral economic demand theory in addiction science has proved useful for evaluating individual characteristics underlying abuse liability. Two factors that have received comparably little attention within this literature are sex and gonadal hormones. We determined cocaine and remifentanil demand in male and female rats using a within-session procedure.

Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

Rationale: Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity.

Objectives: The purpose of the present study was to examine the effects of resistance exercise (i.e.

Adolescent d-amphetamine exposure enhances the acquisition of cocaine self-administration in male and female rats.

Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) has risen drastically over the past 20 years in the United States and abroad. Amphetamine-based prescription stimulants are the most prescribed treatment for ADHD and the diversion of these drugs has also increased. Reports indicate 61% of individuals with an ADHD medication prescription have sold or shared their medication.

Overnight delivery of hypertonic saline by nasal cannula aerosol for cystic fibrosis.

Aim: Inhaled hypertonic saline increases mucociliary clearance, improves pulmonary function, and decreases exacerbations in cystic fibrosis (CF) but contributes to the already significant treatment burden of CF. Overnight delivery of inhaled medications via a specially designed nasal cannula-aerosol device (Trans-nasal Pulmonary Aerosol Delivery [tPAD]) is an alternative approach. Here, we test whether overnight inhalation of hypertonic saline via tPAD improves mucociliary clearance and assess the tolerability of the device.

The effects of social contact on cocaine intake under extended-access conditions in male rats.

Social learning theories of drug use propose that drug use is influenced by the behavior of peers. We previously reported that cocaine self-administration under limited-access conditions can be either facilitated or inhibited by social contact, depending on the behavior of a peer. The purpose of this study was to determine whether social contact influences cocaine self-administration under conditions that are more representative of problematic patterns of drug use.

The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats.

Rationale: Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts.

Objective: The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads.

Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring.

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth weight in offspring, but it can also negatively influence neurodevelopmental outcomes in later stages of life, such as an increased incidence of obesity and drug abuse. Animal models demonstrate that prenatal nicotine (PN) alters the development of the mesocorticolimbic system, which is important for organizing goal-directed behavior.

The effects of resistance exercise on cocaine self-administration, muscle hypertrophy, and BDNF expression in the nucleus accumbens.

Background: Exercise is associated with positive outcomes in drug abusing populations and reduces drug self-administration in laboratory animals. To date, most research has focused on aerobic exercise, and other types of exercise have not been examined. This study examined the effects of resistance exercise (strength training) on cocaine self-administration and BDNF expression, a marker of neuronal activation regulated by aerobic exercise.

Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.

The effects of a shared history of drug exposure on social choice.

Selection theories of drug use propose that individuals choose or self-select into peer groups on the basis of perceived similarities with other group members with regard to their beliefs, attitudes, and histories of drug use. The purpose of the present study was to determine whether a shared history of drug exposure would influence choice of a social partner. Adolescent male rats were treated with either cocaine (3.

Exercise decreases speedball self-administration.

Aims: Epidemiological studies report that individuals who exercise are less likely to abuse drugs. Preclinical studies report that exercise, in the form of treadmill or wheel running, reliably decreases the self-administration of psychomotor stimulants and opioids. To date, preclinical studies have only examined the effects of exercise on responding maintained by individual drugs and not by combinations of multiple drugs.

Cocaine self-administration in social dyads using custom-built operant conditioning chambers.

Background: Traditionally, the analysis of intravenous drug self-administration is limited to conditions in which subjects are tested in isolation. This limits the translational appeal of these studies because drug use in humans often occurs in the presence of others.

New Method: We used custom-built operant conditioning chambers that allowed social dyads visual, olfactory, auditory, and limited tactile contact while concurrently self-administering cocaine.

IV prenatal nicotine exposure increases the reinforcing efficacy of methamphetamine in adult rat offspring.

Background: Maternal smoking during pregnancy is correlated with increased substance use in offspring. Research using rodent models shows that gestational nicotine exposure produces enduring alterations in the neurodevelopment of motivational systems, and that rats prenatally treated with nicotine have altered motivation for drug reinforcement on fixed-ratio (FR) schedules of reinforcement.

Objective: The present study investigated methamphetamine (METH) self-administration in adult offspring prenatally exposed to intravenous (IV) nicotine or saline using a progressive-ratio (PR) schedule of reinforcement.

The effects of social learning on the acquisition of cocaine self-administration.

Background: Social learning models of substance use propose that drug-use behaviors are learned by observing and mimicking the behavior of others. The aim of this study was to examine the acquisition of cocaine self-administration in three groups of experimentally naïve rats: rats that were tested in isolation, rats that were tested in the presence of another rat that had access to cocaine and had previously been trained to self-administer cocaine, and rats that were tested in the presence of another rat that did not have access to cocaine.

Methods: Male rats were reared in isolated or pair-housed conditions and implanted with intravenous catheters.

Intravenous prenatal nicotine exposure increases orexin expression in the lateral hypothalamus and orexin innervation of the ventral tegmental area in adult male rats.

Background: Approximately 18% of pregnant women continue to smoke tobacco cigarettes throughout pregnancy. Offspring exposed to tobacco smoke in utero exhibit a higher incidence of drug use in later stages of development relative to non-exposed children. Animal models indicate that prenatal nicotine (PN) exposure alone alters the development of the mesocorticolimbic dopamine (DA) system, which, in part, organizes motivated behavior and reward.

Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.

In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells.

Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine.

Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenous (IV) exposure method.

Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring.

Background: Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward.

Methods: A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.

Gestational IV nicotine produces elevated brain-derived neurotrophic factor in the mesocorticolimbic dopamine system of adolescent rat offspring.

Maternal smoking during pregnancy is associated with enduring psychopathology, such as increased likelihood of substance use, in offspring. Various animal models demonstrate that continuous nicotine exposure produces teratogenic effects in offspring, as well. In this experiment, a novel intravenous (IV) exposure model was used to determine if gestational nicotine (GN) treatment produced alterations in methamphetamine-induced sensitization and the expression of brain-derived neurotrophic factor (BDNF) in the mesocorticolimbic dopamine (DA) system of adolescent offspring.