TLR3 activation with poly I:C exacerbates escalated alcohol consumption in dependent male C57BL/6J mice.

Activation of TLR3 receptors, which are sensitive to viral infection, has emerged as a possible mechanism that increases alcohol intake in rodents. These studies examined whether a history of ethanol dependence exacerbated the increase in drinking driven by the TLR3 agonist poly I:C. Male C57BL/6J mice (>10 per group) were given access to ethanol (20% v/v) 2 hours a day following a history of home cage drinking or after having been rendered ethanol-dependent using a chronic intermittent ethanol (CIE) vapor model.

The role of oxytocin in alcohol and drug abuse.

The neuropeptide oxytocin (OXT) plays a key role in adaptive processes associated with reward, tolerance, memory and stress responses. Through interactions with brain reward and stress systems, OXT is known to play a role in several neuropsychiatric disorders, particularly those that involve altered social integration, such as alcohol and drug addiction (Heilig et al., 2016).

Rapid alterations in neuroimmune gene expression after acute ethanol: Timecourse, sex differences and sensitivity to cranial surgery.

Prior work has established that that an acute ethanol challenge mimicking high intensity alcohol consumption increased IL-6 and suppressed IL-1β and TNFα mRNA in intoxication, with the opposite pattern seen in withdrawal. These experiments utilized Sprague-Dawley rats to further extend these results across time course (from 45 min to 6 h after ethanol), sex, and central versus peripheral expression. Furthermore, these data show that cannulation surgery may selectively modify the central neuroimmune response to ethanol.

Conditioning the neuroimmune response to ethanol using taste and environmental cues in adolescent and adult rats.

A combined odor and taste cue was paired with a binge-like ethanol exposure (4 g/kg intraperitoneal) using a single-trial learning paradigm. Re-exposure to the CS alone was sufficient to evoke a conditioned Interleukin (IL)-6 elevation in the amygdala in adolescents, an effect that was not observed in young adults. This demonstrates a particular sensitivity of adolescents to alcohol-associated cues and neuroimmune learning, whereas prior work indicated that adults require multiple pairings of ethanol to the CS in order to achieve a conditioned amygdala IL-6 response.

Assessment of Extracellular Cytokines in the Hippocampus of the Awake Behaving Rat Using Large-Molecule Microdialysis Combined with Multiplex Arrays After Acute and Chronic Ethanol Exposure.

Background: Studies have demonstrated persistent changes in central nervous system (CNS) cytokine gene expression following ethanol (EtOH) exposure. However, the low endogenous expression and short half-lives of cytokines in the CNS have made cytokine protein detection challenging. The goal of these studies was to establish parameters for use of large-molecule microdialysis and sensitive multiplexing technology for the simultaneous detection of brain cytokines, corticosterone (CORT), and EtOH concentrations in the awake behaving rat.

The influence of central interleukin-6 on behavioral changes associated with acute alcohol intoxication in adult male rats.

Recent studies have demonstrated brain cytokine fluctuations associated with acute ethanol intoxication (increased IL-6) and withdrawal (increased IL-1β and TNFα). The purpose of the present studies was to examine the potential functional role of increased central interleukin-6 (IL-6). We utilized two tests of ethanol sensitivity to establish a potential role for IL-6 after high (3.

Differential effects of acute versus chronic stress on ethanol sensitivity: Evidence for interactions on both behavioral and neuroimmune outcomes.

Acute alcohol intoxication induces significant alterations in brain cytokines. Since stress challenges also profoundly impact central cytokine expression, these experiments examined the influence of acute and chronic stress on ethanol-induced brain cytokine responses. In Experiment 1, adult male rats were exposed to acute footshock.

Adolescent Ethanol Exposure Leads to Stimulus-Specific Changes in Cytokine Reactivity and Hypothalamic-Pituitary-Adrenal Axis Sensitivity in Adulthood.

Adolescent alcohol use comprises a significant public health concern and is often characterized by binge-like consumption patterns. While ethanol exposure in adulthood has been shown to alter the stress response, including the Hypothalamic-Pituitary-Adrenal (HPA) axis, few studies have examined whether binge-like ethanol exposure during adolescence results in enduring changes in HPA axis sensitivity in adulthood. In the present studies, adolescent Sprague-Dawley rats were given intragastric (i.

A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats.

Our work in Sprague Dawley rats has shown rapid alterations in neuroimmune gene expression (RANGE) in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). These manifest as increased interleukin (IL)-6 and IκBα, and suppressed IL-1β and tumor necrosis factor alpha during acute ethanol intoxication. The present studies tested these effects across the lifespan (young adulthood at 2-3 months; senescence at 18 and 24 months), as well as across strain (Fischer 344) and sex.

Conditioned effects of ethanol on the immune system.

Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g.

Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.

Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene Expression (RANGE), including increased Interleukin (IL)-6 and Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4g/kg) delivered either daily or every-other-day (EOD). Subsequent analyses of blood ethanol concentrations (BECs) and corticosterone were performed to determine whether the schedule of ethanol delivery would alter the pharmacokinetics of, or general sensitivity to, subacute ethanol exposure.

Male adolescent rats display blunted cytokine responses in the CNS after acute ethanol or lipopolysaccharide exposure.

Alcohol induces widespread changes in cytokine expression, with recent data from our laboratory having demonstrated that, during acute ethanol intoxication, adult rats exhibit consistent increases in interleukin (IL)-6 mRNA expression in several brain regions, while showing reductions in IL-1 and TNFα expression. Given evidence indicating that adolescence may be an ontogenetic period in which some neuroimmune processes and cells may not yet have fully matured, the purpose of the current experiments was to examine potential age differences in the central cytokine response of adolescent (P31-33days of age) and adult (69-71days of age) rats to either an acute immune (lipopolysaccharide; LPS) or non-immune challenge (ethanol). In Experiment 1, male Sprague-Dawley rats were given an intraperitoneal (i.