Increased anxiolytic effect in aged female rats and increased motoric behavior in aged male rats to acute alcohol administration: Comparison to younger animals.

The population of most countries in the world is increasing and understanding risk factors that can influence the health of the older population is critical. Older adults consume alcohol often in a risky, binge manner. Previous work has demonstrated that aged rats are more sensitive to many of the effects of acute ethanol. In the current project aged, adult, and adolescent female and male rats were tested on the elevated plus maze and open field following either a 1.0 g/kg alcohol injection or a saline injection. We report sex- and age-dependent effects whereas aged female rats, but not aged male rats, showed an increased anxiolytic effect of alcohol in the elevated plus maze while aged male rats, but not aged female rats, showed increased stimulatory movement in the open field. In addition, significant age effects were found for both female and male rats. It is proposed that the sex- and age-dependent effects reported in the current studies may be due to differential levels of alcohol-induced allopregnanolone for the anxiolytic effects and differential levels of alcohol-induced dopamine for the stimulatory effects. The current work provides insights into factors influencing alcohol consumption in older adults.

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life.

Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.

Old Dog, New Tricks: A Review of Identifying and Addressing Youth Cannabis Vaping in the Pediatric Clinical Setting.

Cannabis vaping has emerged as a predominant mode of cannabis use among United States (US) adolescents and young adults (AYA) primarily due to the popularity of modifiable designs of vaping devices coupled with changes in cannabis policies and increased availability of cannabinoid products. New methods for cannabis vaping by e-liquid/oil vaping, dry plant vaping, and cannabis concentrate vaping (ie, dabbing) have had high uptake among American youth with unclear long-term health implications. Issues with contamination, mislabeling, and expansion of the vaped cannabis market to include not only delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) but also delta-9-THC analogs (eg, delta-8 and delta-10) sold as hemp-derived "legal highs" further complicated this healthcare space. Recent research suggests that cannabis/THC vaping carries distinct and overlapping risks when compared to cannabis smoking and may be associated with greater risk for acute lung injuries, seizures, and acute psychiatric symptoms. Primary care clinicians providing care for AYA are in an ideal position to identify cannabis misuse and intervene early to address cannabis vaping. To improve public health outcomes, a need exists for pediatric clinicians to be educated about different ways/methods that youth are vaping cannabinoid products and associated risks related to cannabinoid vaping. Further, pediatric clinicians need to be trained how to effectively screen for and discuss cannabis vaping with their youth patients. In the current article, we present a clinically focused review of cannabis vaping among young people with 3 main aims to: (1) identify and describe the cannabis vaping products commonly used by American youth; (2) review the health correlates of youth cannabis vaping; and (3) discuss clinical considerations related to identifying and treating youth who vape cannabis.

Using animal models to identify clinical risk factors in the older population due to alcohol use and misuse.

The number of people over the age of 65 years old is increasing and understanding health risks associated with the aged population is important. Recent research has revealed that alcohol (ethanol) consumption levels in older demographics remains elevated and often occurs in a dangerous binge pattern. Given ethical constraints on investigating high level or binge pattern alcohol consumption in humans, animal models are often used to study the effects of ethanol. The current review highlights ongoing work revealing that aged rats are often more sensitive to the effects of acute ethanol compared to younger rats. Specifically, aged rats are more sensitive to the motor impairing, hypnotic, hypothermic, and often the cognitive effects of ethanol compared to younger rats. In addition, the development of ethanol tolerance following chronic exposure may have a different temporal pattern in aged rats compared to younger rats. However, the neurobiological mechanisms that cause the increased sensitivity to ethanol in aged animals have yet to be identified. Furthermore, the differential age effects of ethanol highlight clinical risk factors for alcohol misuse in the older human population. Future work is needed to determine underlying CNS mechanisms producing altered effects of ethanol in aged subjects and also the development of educational material concerning ethanol's effects across ages for health care providers working with the aged population.

Chronic Intermittent Ethanol Administration during Adolescence Produces Sex Dependent Impairments in Behavioral Flexibility and Survivability.

Chronic intermittent ethanol exposure during adolescence produces behavioral impairments and neurobiological changes that can last into young adulthood. One such behavioral impairment is reduced behavioral flexibility, a behavioral impairment that has been correlated with the risk for increased ethanol intake. In the current study, we investigated if chronic intermittent ethanol exposure during adolescence alters cognition, including behavioral flexibility, over a 22-month testing period. Female and male rats were treated with either 3.0 g/kg or 5.0 g/kg ethanol via gavage in a chronic intermittent fashion during adolescence and then tested every 4 to 5 months on a series of cognitive measures in the Morris water maze. Chronic intermittent ethanol selectively impaired behavioral flexibility in both female and male rats, although the pattern of results was different as a function of sex. In addition, female, but not male, rats were impaired in a short-term relearning test. Finally, male rats administered ethanol during adolescence were significantly more likely to not survive the 22-month experiment compared to female rats administered ethanol during adolescence. The current results demonstrate that adolescence is a unique period of development where chronic intermittent ethanol exposure produces long-lasting, selective cognitive impairments across the lifespan.