Kappa-opioid receptor stimulation in the nucleus accumbens shell and ethanol drinking: Differential effects by rostro-caudal location and level of drinking.

Although the kappa-opioid receptor (KOR) and its endogenous ligand, dynorphin, are believed to be involved in ethanol drinking, evidence on the direction of their effects has been mixed. The nucleus accumbens (NAc) shell densely expresses KORs, but previous studies have not found KOR activation to influence ethanol drinking. Using microinjections into the NAc shell of male and female Long-Evans rats that drank under the intermittent-access procedure, we found that the KOR agonist, U50,488, had no effect on ethanol drinking when injected into the middle NAc shell, but that it promoted intake in males and high-drinking females in the caudal NAc shell and high-drinking females in the rostral shell, and decreased intake in males and low-drinking females in the rostral shell.

Sex-related differences in endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) in the thalamic paraventricular nucleus: Implications for addiction neuroscience.

Males and females exhibit differences in motivated and affective behavior; however, the neural substrates underlying these differences remain poorly understood. In the paraventricular nucleus of the thalamus (PVT), sex-related differences in neuronal activity have been identified in response to motivated behavior tasks and affective challenges. Within the PVT, the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is highly expressed and is also involved in motivated and affective behavior.

Sex differences in cognitive flexibility are driven by the estrous cycle and stress-dependent.

Stress is associated with psychiatric disorders such as post-traumatic stress disorder, major depressive disorder, anxiety disorders, and panic disorders. Women are more likely to be diagnosed with these stress-related psychiatric disorders than men. A key phenotype in stress-related psychiatric disorders is impairment in cognitive flexibility, which is the ability to develop new strategies to respond to different patterns in the environment.

Inactivation of the thalamic paraventricular nucleus promotes place preference and sucrose seeking in male rats.

Rationale: The experience of reward entails both positive affect and motivation. While the brain regions responsible for these distinct aspects of reward are dissociable from each other, the paraventricular nucleus of the thalamus (PVT) may play a role in both.

Objectives: To investigate the role of the PVT in both affect and motivation, and to identify neuropeptides that might mediate these effects.

Stress, coping, resilience, and sleep during the COVID-19 pandemic: A representative survey study of US adults.

Introduction: The COVID-19 pandemic is a global health emergency resulting in widespread death and substantial disruption to daily life. Previous research has shown that novel disease outbreaks are associated with high stress levels and sleep impairments that lead to neuropsychiatric consequences. Therefore, it is vital to study both stress and protective factors such as coping and resilience that may hinder or help sleep quality during the COVID-19 pandemic.

Sex differences in stress-induced sleep deficits.

Sleep disruptions are hallmarks in the pathophysiology of several stress-related disorders, including Major Depressive Disorder (MDD) and Post-Traumatic Stress Disorder (PTSD), both known to disproportionately affect female populations. Although previous studies have attempted to investigate disordered sleep in women, few studies have explored and compared how repeated stress affects sleep in both sexes in either human or animal models. We have previously shown that male rats exhibit behavioral and neuroendocrine habituation to 5 days of repeated restraint, whereas females do not; additional days of stress exposure are required to observe habituation in females.

Effects of pituitary adenylate cyclase-activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking.

While limited research has implicated the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in problematic alcohol use, the brain regions and isoforms involved in this effect remain to be determined. One region that has been found both to exhibit PACAP binding and, separately, to be involved in ethanol drinking is the nucleus accumbens (NAc). Thus, this study sought to characterize the effect of the PACAP isoforms in the NAc on ethanol drinking under the intermittent-access two-bottle-choice paradigm, in male and female Long-Evans rats.

Kappa-opioid receptor-dependent changes in dopamine and anxiety-like or approach-avoidance behavior occur differentially across the nucleus accumbens shell rostro-caudal axis.

Neural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote aversion, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses.

Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm.

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented.

Pleiotropic pituitary adenylate cyclase-activating polypeptide (PACAP): Novel insights into the role of PACAP in eating and drug intake.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was discovered thirty years ago, but its role in eating and drug use disorders has only recently begun to be investigated. The present review develops the hypothesis that, although PACAP normally functions to tightly regulate intake, inhibiting it through negative feedback, this relationship can become dysregulated with the development of dependence, such that PACAP instead acts through positive feedback to promote excessive intake. We propose that repeated exposure to palatable food and drugs of abuse can alter the downstream responses of specific populations of neurons to stimulation by PACAP, leading to the perpetuation of the addiction cycle.

Pituitary Adenylate Cyclase-Activating Polypeptide-27 (PACAP-27) in the Thalamic Paraventricular Nucleus Is Stimulated by Ethanol Drinking.

Background: The paraventricular nucleus of the thalamus (PVT) is a limbic brain structure that affects ethanol (EtOH) drinking, but the neurochemicals transcribed in this nucleus that may participate in this behavior have yet to be fully characterized. The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is known to be transcribed in other limbic areas and to be involved in many of the same behaviors as the PVT itself, possibly including EtOH drinking. It exists in 2 isoforms, PACAP-38 and PACAP-27, with the former expressed at higher levels in most brain regions.

Methylphenidate Enhances Early-Stage Sensory Processing and Rodent Performance of a Visual Signal Detection Task.

Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance-enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action affects neural circuits performing cognitive and sensorimotor functions driving performance enhancement.