Modeling Adolescence in Rodents
Much of our research examines adolescent alcohol sensitivity, intake and consequences using a simple non-human animal model, the rat. Although of course no species shows the rich complexity of brain/behavioral function as seen in the human, a number of commonalities are seen across a wide variety of species in the physiological, brain and cognitive/behavioral changes occurring during the adolescent-typical transition from dependence to (relative) independence.
Across-species behavioral similarities.
Adolescent rats relative to their adult counterparts often: (a) engage in more peer directed social interactions and view these interactions to be particularly rewarding; (b) show increases in novelty-seeking and risk-taking behaviors, and find novel stimuli particularly rewarding; and (c) exhibit elevated intake of alcohol in a variety of situations.
Brain similarities across species.
The basic structures, functions, and cellular and molecular components of the brain are similar across mammalian species, along with the relative timing of changes in different brain regions across the life-span. Thus, many of the developmental transformations of adolescence seen in humans are also evident, in sometimes simplified form, in the brains of rats undergoing this developmental transition as well.
Why use animal models?
While rapidly evolving technology for imaging the human brain provides exciting opportunities for study of the adolescent brain, this technology does not permit examination of morphological and molecular underpinnings of observed age-related differences in brain structure and activity nor causal relationships between brain maturation and behavior -- including neural contributors to, and consequences of risky behavior patterns including drug/alcohol use. It is possible to examine these critical issues via studying adolescence using animal models such as the rat. Animal models also permit assessment of consequences of adolescent alcohol and drug exposures that typically cannot be studied in young (underage) human adolescents.
Ongoing Research Activities
Impact of Acute and Chronic Tolerance on Adolescent Alcohol Consumption.
Adolescents appear less sensitive to many alcohol effects in part because their brains adapt so readily to the presence of alcohol within a single alcohol exposure period, a phenomenon known as acute tolerance. The goals of this project are to determine the relationship between alcohol consumption and the development of acute tolerance and (more slowly developing) chronic tolerance to various effects of ethanol during adolescence and in adulthood, to explore neural substrates underlying these ethanol adaptations, and to assess whether tolerance development is causal for inducing the high levels of alcohol consumption characteristic of adolescence. Ethanol effects that we are exploring include motor impairing and other aversive effects of alcohol as well as age differences in alcohol's effects on vagal tone and the autonomic nervous system.
Social Facilitation and Ethanol Reward in Adolescence.
Our prior work in this area has shown that low doses of alcohol markedly increase social behavior in adolescent rats whereas this effect is not normally evident in mature animals. This project explores the social neuroscience of adolescent alcohol use to determine whether alcohol enhances the rewarding properties of social stimuli to make them particularly rewarding for adolescents, and/or whether alcohol exposure in a social context increases the rewarding properties of alcohol more dramatically during adolescence than in adulthood.
Alcohol, Puberty and Sex Differences.
Our studies in this area are to determine the impact of puberty on sex- and age- differences in alcohol intake, alcohol sensitivity, and alcohol/stress interactions. In this work, we are investigating the effects of gonadectomy (castration; ovariectomy) either prior to puberty or in adulthood on ethanol intake and sensitivity to various ethanol effects, and whether resulting effects are reversed by administration of replacement hormones.
Role of GABAA and NMDA Receptor Systems in Adolescent Alcohol Sensitivities.
In earlier work, we have shown that adolescents are less sensitive to aversive and intoxicating effects appearing at moderate or higher doses of alcohol (such as alcohol's social impairing, coordination disrupting, and sedative effects). Thus, the greater alcohol consumption levels seen in adolescent rats relative to adult rats (as in human adolescents) may be in part because they can – that is, they may be able to drink more than adults because of their resistance to alcohol effects that may normally serve as feedback cues to limit consumption. On the other hand, adolescents appear more sensitive to certain rewarding effects of alcohol, including the facilitation in social behavior induced at relatively low doses of alcohol. In this project, we are examining the roles of NMDA and GABAA receptors in adolescent-specific insensitivities to aversive effects of alcohol, as well as the greater sensitivity that adolescents show to the social facilitating effects of alcohol. We are also exploring the role of these receptors in age differences in the interoceptive consequences of alcohol as revealed by a drug discrimination procedure.
Impact of adolescent alcohol consumption on social anxiety and alcohol relief from social anxiety in adulthood.
In this project, we are examining lasting consequences of adolescent alcohol exposure – looking at both consequences of voluntary alcohol use as well as comparable amounts of alcohol exposure via experimenter-administered alcohol. We are specifically testing the hypothesis that adolescent alcohol use may be particularly likely to induce long-lasting increases in social anxiety, encouraging alcohol intake for its anxiolytic properties. We will also be exploring underlying neural/genetic adaptations.
Adolescence as a time of increased vs. decreased reward sensitivities.
We have a long-standing interest in the question of whether adolescents exhibit increases in behaviors directed towards natural rewards, alcohol and drugs of abuse because they find these stimuli highly rewarding and thereby avidly pursue them, or because they are attempting to compensate for an age-related reward insensitivity by increasing their "consumption" of these rewards. Data to date have revealed intriguing complexities in adolescent reward sensitivity that we continue to pursue using assessment of ultrasound production and other approaches to index hedonic sensitivity.
Field work in human adolescents: the Collaborative Ethanol Group (CEG) project.
In this work, we are collaborating with the laboratory of Dr, Steve Lisman, a clinical psychologist in our department and Dr. Gerard Johansen, an alcohol counselor at the university. In CEG, we are obtaining self-report data on perceived alcohol effects, problems, and motives for drinking, as well as breathalyzer samples (BALs), cognitive and motor performance data, and DNA samples from 18-30 year old drinkers in a mobile laboratory located outside of a local bar area. Included among the goals of this work are to assess whether attenuated sensitivities to motor impairing effects of alcohol seen in our rodent studies are also evident in these samples of older adolescents.