Late aging alters behavioral sensitivity to ethanol in a sex-specific manner in Fischer 344 rats

Abstract

Responsiveness to ethanol (EtOH) differs as a function of age. Adolescent rodents are less sensitive than adults to the sedative effects of EtOH, whereas they show enhanced sensitivity to EtOH-induced social facilitation. Late aging is associated with a natural decline in social behavior and aging-related peculiarities in sensitivity to EtOH have been largely unexplored. Whether there are sex differences in the behavioral response to EtOH during late aging remains unknown. Thus, behavioral responses to EtOH in male and female Fischer (F) 344 rats aged 4-5 months (adult) and 19-20 months (aging) were examined. First, the effects of saline and EtOH (0.5 and 0.75 g/kg) on social interaction were assessed. Social investigation and contact behavior were lower in aging animals and higher in females. Interestingly, in aged females, social contact behavior was increased following a 0.5 g/kg EtOH dose, whereas the same dose suppressed social contact in aged males. Behavioral sensitivity to the sedative effects of 3.0 and 3.5 g/kg EtOH was assessed with the loss of righting reflex (LORR) test. Although latency to LORR did not differ as a function of age or sex, aged rats showed significantly greater LORR duration and significantly lower blood ethanol concentrations (BECs) at regaining of the righting reflex relative to adults. In addition, females had a lower LORR duration, regardless of age; no sex differences were evident in BECs at awakening. In a second experiment, blood ethanol concentrations (BECs) over time were assessed following 0.75, 1.5, and 3.0 g/kg EtOH in 3-, 12-, and 18-month-old male and female F344 rats. Aged rats had higher peak BECs following 3.0 g/kg EtOH, whereas few age or sex differences were apparent at lower doses. Taken together, these data indicate that late aging is associated with altered sensitivity to the social facilitating effects and sedative effects of EtOH.

Sex and Age Effects on Neurobehavioral Toxicity Induced by Binge Alcohol

“…One of the few studies to address sex differences in alcohol effects in older animals looked at social interaction, as well as ethanol sensitivity as a function of age and sex, by examining latency and duration of the loss of righting reflex (LORR) following i.p. injection of ethanol [86]. In adult males and females, injection of 0.5 or 0.75 g/kg of ethanol decreased social behavior.…”

Aging in nucleus accumbens and its impact on alcohol use disorders

“…Regarding studies in animal models, the main effects of alcohol that have been evaluated are cognition, ataxia, hypothermia, and sedation. In the latter three, an age-dependent increase was observed when comparing adolescent, adult, and aged animals ( Matthews et al, 2019 ; Ornelas, Novier, Van Skike, Diaz-Granados, & Matthews, 2015 ; Perkins, Vore, Lovelock, Varlinskaya, & Deak, 2018 ; Silveri & Spear, 2000 ; Van Skike et al, 2010 ; Watson, James, Mittleman, & Matthews, 2020 ). In studies where the effects on cognition were tested, specifically spatial memory tests, no differences were observed between adolescent and adult animals following an acute dose of alcohol ( Chin et al, 2011 ; Matthews, Scaletty, Schreiber, & Trapp, 2020 ); however, aged animals did show impairment on memory tasks in general, both those assessing spatial and non-spatial memory ( Matthews et al, 2020 ).…”

“…Furthermore, sex differences in the behavioral response to ethanol were observed in aged rats. For instance, aged females, but not males, exhibited social facilitation after intraperitoneal injection of low doses of ethanol ( Perkins et al, 2018 ). However, there are no available data demonstrating sex differences in alcohol intake in older animals and even less about underlying mechanisms.…”

Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer’s Disease

“…Alcohol use has been high or rising in most demographics including adolescents, young adults, and older females without children . However, compared to younger drinkers, the percentage of older adult drinkers has had a greater escalation in recent years, and older adults often consume alcohol in a hazardous binge drinking pattern. − Recent preclinical research has demonstrated that aged rodents are more sensitive to the effects of acute ethanol exposure compared to younger adult rodents. − Furthermore, chronic intermittent ethanol exposure (CIEE), a model of binge-like ethanol consumption, may produce tolerance to a high-dose ethanol challenge in aged animals faster than in younger adult animals and impair cognition late in life. , Given the increases in the percentages of drinkers and the engagement of more hazardous consumption patterns in the aged population, understanding the potential negative impacts of alcohol on the aged is critical.…”

“… 10 − 14 Recent preclinical research has demonstrated that aged rodents are more sensitive to the effects of acute ethanol exposure compared to younger adult rodents. 15 − 20 Furthermore, chronic intermittent ethanol exposure (CIEE), a model of binge-like ethanol consumption, may produce tolerance to a high-dose ethanol challenge in aged animals faster than in younger adult animals 21 and impair cognition late in life. 15 , 22 Given the increases in the percentages of drinkers and the engagement of more hazardous consumption patterns in the aged population, understanding the potential negative impacts of alcohol on the aged is critical.…”