Alcohol (Hanover, York County, Pa.)最新文献

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.

Methods: Adult, female Long-Evans rats were injected in the PVT with an adeno-associated virus (AAV) to increase expression of PACAP or a control AAV. They were then investigated for subsequent ethanol drinking and preference; sucrose drinking and preference; or locomotor activity in a novel chamber, behavior in a light-dark box, behavior in a novelty suppression of feeding test, locomotor activity in a familiar activity chamber, and behavior in a forced swim test.

Results: Injection with the PACAP AAV resulted in a specific increase in levels of PACAP-27. Rats injected with the PACAP AAV demonstrated reduced drinking and preference for ethanol under the intermittent-access procedure compared to those injected with the control AAV. In contrast, rats injected with the PACAP AAV showed no significant difference in drinking or preference for sucrose, or in any affective behavior tested, except that they spent less time swimming in the forced swim test.

Conclusions: In light of the low overall level of expression of PACAP-27 in the brain, the ability of PACAP-27 in the PVT to control ethanol drinking, with minimal effects on other motivated or affective behaviors, supports the idea that compounds related to PACAP-27 should be investigated as potential therapeutics for the treatment of alcohol use disorder.

Background: Alcohol-associated hepatitis (AH) is a subtype of alcohol-associated liver disease (ALD) resulting in severe acute liver inflammation. This study aims to examine longitudinal trends in mortality from AH in the United States (US) from 1999 to 2020, stratifying the data by sex, age, and racial/ethnic groups.

Methods: We performed a cross-sectional study using data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) to determine annual AH-related mortality rates (MR) in adults ≥21 years between 1999 and 2020. Data were stratified by sex, race, and 10-year age groups. Considering 1999 as baseline, mortality rate ratio (MRR) was calculated to characterize the MR in a particular year compared to baseline. Joinpoint regression analysis was conducted to characterize year-wise log-linear time calendar trends in MR.

Results: From 1999 through 2020, AH-related deaths doubled from 0.5 per 100,000 (95% CI 0.5 to 0.6) to 1.1 per 100,000 (95% CI 1.1 to 1.2). While mortality rates for males doubled from 0.8 per 100,000 (95% CI 0.7 to 0.8) to 1.5 per 100,000 (95% CI 1.4 to 1.6), mortality rates for females almost tripled from 0.3 per 100,000 (9%% CI 0.3 to 0.4) to 0.8 per 100,000 (95% CI 0.7 to 0.8). The steepest increase in AH-related deaths from 1999 to 2020 were among American Indians/Alaska Natives and young adults 25-34 years, and particularly young adult females.

Conclusions: Over the past two decades, overall AH-related mortality in the US has doubled. The steepest increase in AH-related mortality was noted among American Indians/Alaska Natives and young adults, particularly young adult females. Education and prevention efforts should target these high-risk populations, and studies aimed at elucidating biological and sociodemographic factors resulting in the differential rise in mortality are warranted.

Background: Fine motor skill deficits have been reported for children with histories of prenatal alcohol exposure, but little is known whether impaired motor skill extends to the regulation of precision grip control.

Methods: Children with (n = 15) and without (n = 17) histories of heavy prenatal alcohol exposure used their dominant hand to grasp, lift, and hold in space a small-instrumented object with a mass of 19 g. Object mass was also experimentally increased by separately adding two aluminum cubes with mass of 200 and 400 g. Participants completed a block of eight trials for each object mass with the last six trials in each trial block being statistically analyzed. Selected temporal and kinetic parameters of grip force (GF) and load force (LF) were examined to quantitatively index precision grip performance of the two groups.

Results: Compared to typically developing peers, children with prenatal alcohol exposure used excessive and more variable LF and greater GF to lift each object mass, with more finger GF than thumb GF being applied to the apparatus. The GF/LF ratio for the clinical group was greater when lifting the smallest mass load. When holding the object in space, children with prenatal alcohol exposure produced greater GF for the smallest mass load, again with more GF being applied via the finger compared to the thumb.

Conclusions: Children with heavy prenatal alcohol exposure demonstrate force deficits when using precision grip to manipulate an object with three different masses. Chronic irregular precision grip could manifest as a fine motor skill developmental delay that may negatively impact completion of functional activities of daily living requiring grasping an object with the index finger and thumb.

Background: One trait of alcohol use disorder (AUD) is continuing to drink despite negative consequences. The current study investigated initial/early aversion-resistant drinking (ARD) across selectively bred alcohol-preferring lines to assess aversion resistance with minimal ethanol history and subsequent ethanol-seeking and drinking profiles. Additionally, ARD was assessed in alcohol-preferring and non-preferring rats using a sucrose reinforcer to determine if ARD may be a genetic risk factor for AUD.

Methods: Male and female alcohol-preferring rats were given four concentrations of quinine (0.03, 0.10, 0.30, and 1.00 g/L-in random order) in an ethanol solution in the homecage for 30 min daily across 12 days. Seeking and drinking were then assessed in the operant chambers. Additional groups of alcohol-preferring and non-preferring rats were given access to the same concentrations of quinine-adulterated sucrose using the same daily, random-order presentation.

Results: In ethanol, all preferring lines performed similarly, showing resistance to quinine at the lowest concentration. In the homecage, high-alcohol-drinking (HAD)1 rats drank high levels of ethanol similar to alcohol-preferring (P) rats, whereas in an operant task were more similar to the HAD2 rats. In sucrose, P and HAD2 rats were shown to be aversion resistant at low concentrations of quinine compared to baseline. Overall, the non-preferring lines all demonstrated sensitivity to quinine-adulterated sucrose.

Conclusions: This study demonstrates alcohol-preferring lines show similar ARD when ethanol is the reinforcer. Regarding motivated responding, P rats show high-seeking and drinking behaviors as previously observed. In the homecage, HAD1 rats drink similarly to P rats indicating that different conditions (i.e., free vs. operant access) influence drinking behaviors between these lines. Importantly, in a sucrose reinforcer, alcohol-preferring rats are more aversion-resistant than non-preferring lines, while non-preferring lines show high sensitivity to aversion, suggesting an overall tendency to demonstrate a low level of compulsive behavior.

Background: Adolescent alcohol use is the norm, but only some develop a substance use disorder. The increased risk might reflect heightened mesocorticolimbic responses to reward-related cues but results published to date have been inconsistent.

Methods: Young social drinkers (age 18.5 ± 0.6 y.o.) who have been followed since birth were recruited from high- versus low-risk trajectories based on externalizing (EXT) behavioral traits. All had functional magnetic resonance imaging (fMRI) scans to measure mesocorticolimbic responses to alcohol, juice, and water cues (High EXT: 20F/10M; Low EXT: 15F/12M). Most had positron emission tomography (PET) [¹⁸F]fallypride scans to measure brain regional dopamine D2 receptor availabilities (n = 47).

Results: Compared with the low EXT group, high EXT participants reported larger subjective responses to the alcohol and juice cues (vs. water). Despite this, a main effect of group was not seen for brain activation responses to the alcohol and juice cues. Instead, low EXT participants exhibited higher mesocorticolimbic activations to alcohol than juice, whereas these activations did not differ in the high EXT group. Across all participants, alcohol (vs. water) blood oxygen level-dependent (BOLD) responses in the striatum and amygdala were associated with midbrain [¹⁸F]fallypride BP_ND values.

Conclusion: Young social drinkers at high versus low risk for substance use disorders did not exhibit larger mesocorticolimbic BOLD activations to alcohol-related cues and their responses poorly differentiated alcohol from juice. These observations raise the possibility that (i) diminished mesocorticolimbic BOLD differentiations between reward-related cues might be a marker of increased risk for substance use disorders, and (ii) previously reported large BOLD responses to drug-related cues in people with substance use disorders might better identify the disease than pre-existing vulnerability.