Morphine-context associative memory and locomotor sensitization in mice are modulated by sex and context in a dose-dependent manner.

Sex differences in opioid use, development of opioid used disorder, and relapse behaviors indicate potential variations in opioid effects between men and women. The locomotor and interoceptive effects of opioids play essential roles in opioid addiction, and uncovering the neural mechanisms underlying these effects remain crucial for developing effective treatments. In this study, we examined the dose-dependent effects of morphine on locomotor sensitization and the strength and stability of morphine-context associations in the conditioned place preference (CPP) paradigm in male and female mice, as well as the relationships between these measures.

Cyfip2 allelic variation in C57BL/6J and C57BL/6NJ mice alters free-choice ethanol drinking but not binge-like drinking or wheel-running activity.

Background: Since the origin of the C57BL/6 (B6) mouse strain, several phenotypically and genetically distinct B6 substrains have emerged. For example, C57BL/6J mice (B6J) display greater voluntary ethanol consumption and locomotor response to psychostimulants and differences in nucleus accumbens synaptic physiology relative to C57BL/6N (B6N) mice. A non-synonymous serine to phenylalanine point mutation (S968F) in the cytoplasmic FMR1-interacting protein 2 (Cyfip2) gene underlies both the differential locomotor response to cocaine and the accumbal physiology exhibited by these substrains.

Circuit and neuropeptide mechanisms of the paraventricular thalamus across stages of alcohol and drug use.

The paraventricular nucleus of the thalamus (PVT) is a midline thalamic brain region that has emerged as a critical circuit node in the regulation of behaviors across domains of affect and motivation, stress responses, and alcohol- and drug-related behaviors. The influence of the PVT in this diverse array of behaviors is a function of its ability to integrate and convey information about salience and valence through its connections with cortical, hypothalamic, hindbrain, and limbic brain regions. While understudied to date, recent studies suggest that several PVT efferents play critical and complex roles in drug and alcohol-related phenotypes.

Photic Regulation of Circadian Rhythms and Voluntary Ethanol Intake: Role of Melanopsin-expressing Intrinsically Photosensitive Retinal Ganglion Cells.

"Non-image-forming" (NIF) effects of light are mediated primarily by a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment, melanopsin (OPN4). These NIF functions include circadian entrainment, pupillary reflexes, and photic effects on sleep, mood, and cognition. We recently reported that mice of multiple genotypes exhibit reduced voluntary ethanol intake under both constant darkness (DD) and constant light (LL) relative to standard light-dark (LD) conditions.

Affective Disruption During Forced Ethanol Abstinence in C57BL/6J and C57BL/6NJ Mice.

Background: In alcohol-dependent individuals, acute alcohol withdrawal results in severe physiological disruption, including potentially lethal central nervous system hyperexcitability. Although benzodiazepines successfully mitigate such symptoms, this treatment does not significantly reduce recidivism rates in postdependent individuals. Instead, persistent affective disturbances that often emerge weeks to months after initial detoxification appear to play a significant role in relapse risk; however, it remains unclear whether genetic predispositions contribute to their emergence, severity, and/or duration.

Suppression of voluntary ethanol intake in mice under constant light and constant darkness.

Seasonal variations in photoperiod are associated with alterations in human mood and behavior. Similarly, manipulation of the environmental lighting regimen can exert pronounced effects on affective behavior in experimental animals. These observations may be due, in part, to light-induced alterations in circadian rhythms, but it seems likely that other, non-circadian factors also contribute.

Affective Behavior in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant Mice during Long-Term Alcohol Abstinence.

Background: While the acute alcohol withdrawal syndrome has been well characterized both in human clinical studies and in experimental animals, much less is known regarding long-term affective disturbances that can sometimes persist during protracted abstinence. Nevertheless, since relapse often occurs long after acute detoxification and may be predicted by persistent affective disruption, a better understanding of the long-term behavioral consequences of prior alcohol dependence may lead to improved strategies for relapse prevention.

Methods: Male and female Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice from the second selection replicate (WSP-2, WSR-2) were exposed to a 10-day chronic-intermittent ethanol vapor protocol (CIE) or plain air and then tested repeatedly on the sucrose preference test (SPT), marble burying test (MBT), and the light-dark box test (LDT) over 7 weeks of (forced) abstinence.