Effects of isolation stress and voluntary ethanol exposure during adolescence on ethanol and nicotine co-use in adulthood using male rats.

Background: Alcohol use in adolescence may increase susceptibility to substance use disorders (SUDs) in adulthood. This study determined if voluntary ethanol (EtOH) consumption during adolescence, combined with social isolation, alters the trajectory of EtOH and nicotine intake during adulthood, as well as activating brain neuroinflammation.

Methods: Adolescent male isolate- and group-housed rats were given 0.

Targeting α- and α-adrenergic receptors as a countermeasure for fentanyl-induced locomotor and ventilatory depression.

This study assessed the ability of α and α-adrenergic drugs to decrease fentanyl-induced locomotor and ventilatory depression. Rats were given saline or fentanyl, followed by: (1) naltrexone, (2) naloxone, (3) nalmefene, (4) α agonist phenylephrine, (5) α antagonist prazosin, (6) α antagonist BMY-7378, (7) α agonist clonidine, (8) α antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression.

Vesicular monoamine transporter-2 inhibitor JPC-141 prevents methamphetamine-induced dopamine toxicity and blocks methamphetamine self-administration in rats.

Previous research has demonstrated therapeutic potential for VMAT2 inhibitors in rat models of methamphetamine use disorder. Here, we report on the neurochemical and behavioral effects of 1-(2-methoxyphenethyl)-4-phenethypiperazine (JPC-141), a novel analog of lobelane. JPC-141 potently inhibited (Ki = 52 nM) [H]dopamine uptake by VMAT2 in striatal vesicles with 50 to 250-fold greater selectivity for VMAT2 over dopamine, norepinephrine and serotonin plasmalemma transporters.

Adolescent Intermittent Ethanol Drives Modest Neuroinflammation but Does Not Escalate Drinking in Male Rats.

During adolescence, the brain is highly susceptible to alcohol-induced damage and subsequent neuroimmune responses, effects which may enhance development of an alcohol use disorder (AUD). Neuroimmune reactions are implicated in adolescent alcohol exposure escalating adulthood drinking. Therefore, we investigated whether intermittent alcohol exposure in male, adolescent rats (AIE) escalated adult drinking via two-bottle choice (2BC).

Effects of voluntary adolescent intermittent alcohol exposure and social isolation on adult alcohol intake in male rats.

Initiating alcohol use in adolescence significantly increases the likelihood of developing adult alcohol use disorder (AUD). However, it has been difficult to replicate adolescent alcohol exposure leading to increased adult alcohol intake across differing preclinical models. In the present study, differentially housed male rats (group vs.

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood.

Effects of adolescent alcohol exposure via oral gavage on adult alcohol drinking and co-use of alcohol and nicotine in Sprague Dawley rats.

Background: Preclinical models simulating adolescent substance use leading to increased vulnerability for substance use disorders in adulthood are needed. Here, we utilized a model of alcohol and nicotine co-use to assess adult addiction vulnerability following adolescent alcohol exposure.

Methods: In Experiment 1, adolescent (PND30) male and female Sprague-Dawley rats received 25% ethanol (EtOH) or a control solution via oral gavage every 8 h, for 2 days.

Modulation of relapse-like drinking in male Sprague-Dawley rats by ligands targeting the α5GABA receptor.

Preclinical evidence suggests a key role for GABA receptors containing the α5 subunit (i.e., α5GABA receptors) in the abuse-related effects of alcohol, including the reinforcing and discriminative stimulus effects, as well as cue-induced alcohol-seeking behavior.

Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking.

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear.

Effects of ethanol, naltrexone, nicotine and varenicline in an ethanol and nicotine co-use model in Sprague-Dawley rats.

Background: As alcohol and nicotine use disorders are entwined, it may be possible to develop a single medication to treat both. We previously developed a model for ethanol (EtOH) and nicotine co-use in female selectively bred alcohol-preferring (P) rats. To model co-use in a genetically diverse population, we adapted the model to outbred Sprague-Dawley rats of both sexes and assessed the effect of drug pretreatments.

Changes in the elimination and resurgence of alcohol-maintained behavior in rats and the effects of naltrexone.

Resurgence may be a mechanism of relapse in alcohol use disorder patients upon discharge from treatment as part of an abuse-treatment-relapse cycle. Adjunctive pharmacotherapies may be a means to facilitate behavioral treatments and block resurgence. Experiments were conducted using a model of alcohol self-administration to assess the repeatability of the elimination and resurgence of alcohol-maintained behavior and the effects of naltrexone.

Correction to: GABA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence.

The chemical name appearing in the first column of Table 1 on the 3 row from bottom of the table is wrong.

α5GABA subunit-containing receptors and sweetened alcohol cue-induced reinstatement and active sweetened alcohol self-administration in male rats.

Rationale: GABA receptors containing the α5 subunit (i.e., α5GABA receptors) appear to be critically involved in the reinforcing and subjective effects of alcohol.

GABA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence.

Ethanol's reinforcing and subjective effects, as well as its ability to induce relapse, are powerful factors contributing to its widespread use and abuse. A significant mediator of these behavioral effects is the GABA receptor system. GABA receptors are the target for γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS.

Persistent negative effects of alcohol drinking on aspects of novelty-directed behavior in male rhesus macaques.

Humans with histories of prolonged heavy alcohol use exhibit poorer performance on cognitive tasks associated with problem solving, short-term memory, and visuospatial reasoning, even following the cessation of drinking, when compared with healthy controls. It is unclear, however, whether the cognitive problems are a consequence of alcohol exposure or a contributing factor to alcohol-use disorders. Here, we examined the relationship between performance on a novel object recognition (NOR) task and total alcohol consumption (TAC) in adult male rhesus macaques (n = 12; ETH group; trained to self-administer alcohol).