Drinking Typography Established by Scheduled Induction Predicts Chronic Heavy Drinking in a Monkey Model of Ethanol Self‐Administration

Abstract

Background-We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption.

Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders

“…Notably, we found that rapamycin attenuates "binge-like" alcohol drinking behavior. This last finding is of particular interest because binge drinking is an increasingly prevalent problem during adolescence and young adulthood, and is a strong predictor of future alcohol-related problems (40,41). Our findings are also relevant for the treatment of alcoholism, in which the pattern of alcohol consumption is often characterized by successive cycles of daily episodes of binge drinking and withdrawal (25).…”

In vitroandin vivomodels of acute alcohol exposure

“…One important feature of AAA models is the definition of biologically meaningful levels of alcohol, either in vitro or in vivo, and their relationship to blood alcohol levels (BAL) in humans. This is an important requirement of the research models of AAA, because BAL can be detected as soon as minimal amounts of alcohol are ingested [85] , however measurable affects of alcohol on physiology and/or behavior is established at 0.08% or above this level, with individual variations depending on the species, metabolic particularities, age, gender and genetic background [86][87][88][89][90][91][92][93][94][95][96][97] . It is also important to identify that AAA models differ by their route of alcohol delivery to achieve alcohol intoxication, some of them being physiological, such as oral administration, while others being non-physiological, when ethanol is administered by parenteral routes.…”

“…Among non-human vertebrates commonly involved in alcohol research are primates [90,91,148] , pigs [104,120] , dogs [114,121] , mice [70,72,74,86,89,96,109,118,119,141] , rats [88,94,108,149,150] and rabbits [132] . The rodent AAA models (mice and rats) are used most frequently due to their relatively well-defined genetic background and the availability of diverse genetic traits, including those coding for high or low alcohol consumption [88,89,96,109] .…”

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

“…Dams were trained to orally selfadminister either 1.5g/kg/day of 4% ethanol solution (equivalent to 6 drinks/day) or an isocaloric control fluid following a previously described 4-month schedule induced polydipsia procedure 20,21,23 . Following drinking induction, plasma estradiol and progesterone levels were sampled daily until ovulation was suspected, at which point dams were paired with male animals.…”

“…Maternal smoking, nutritional inadequacy, medication or illicit drug use, all factors that can have a synergistic effect on alcohol exposure, often confound human studies of placental impairment. Modeling human drinking behavior with NHP models provides the added advantage of a precise alcohol history 20,21 while retaining the normal route of alcohol administration as opposed to strategies used to study fetal ethanol exposure in rodents. Further, voluntary ethanol selfadministration also obviates the need for procedures such as gavage, which introduce confounds associated with increased maternal stress 22 .…”