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
Our basic science laboratory uses a simple animal model (the rat) to address critical research questions
WHY DO ADOLESCENTS CONSUME MORE ALCOHOL PER OCCASION (i.e., BINGE DRINK) AT HIGHER RATES THAN DO ADULTS?
Adolescent rats, like their human counterparts, often drink more per occasion than do adults. While rodent adolescents rarely drink enough to reach blood ethanol concentrations (BECs) commensurate with human binge level ethanol consumption (i.e., BECs > .08 g/dl), we have developed a binge drinking model where adolescent rats voluntary drink alcohol, often to above binge levels, in 30 minute daily intake tests. Using this model as well as experimenter-administered ethanol challenges, our research as well as that of others has shown that adolescents drink more alcohol in part because they can – that is they are less sensitive to consequences of alcohol (including its motor impairing, sedative and aversive effects) that normally serve as negative feedback cues to terminate drinking.
HOW AND WHY DO ADOLESCENTS RESPOND DIFFERENTLY TO ALCOHOL THAN DO ADULTS?
Adolescent rats are not only less sensitive than are adults to undesired ethanol effects that can serve as cues to terminate drinking as mentioned above, but they are more sensitive to certain desired effects of ethanol – specifically ethanol's reinforcing effects and ethanol-induced social facilitation. Brain regions and neurotransmitter systems contributing to these notable age differences have been and are being explored in our laboratory. Areas of particular interest include alterations in excitatory (glutamate)/inhibitory (GABA) balance and NMDA and GABA-R expression, as well as developmental changes in opiate (kappa) receptors and oxytocin/vasopressin systems. We are also currently using c-fos LacZ transgenic rats to examine the role of regional ensemble activation in the greater aversive consequences of alcohol in adolescent animals. In these and other projects, we frequently collaborate with the laboratories of Drs. Varlinskaya and Werner, among others.
DO MALE AND FEMALE ADOLESCENTS DIFFER IN CONTRIBUTORS TO DRINKING ALCOHOL IN A SOCIAL CONTEXT?
We have shown that adolescent female (but not male) rats that are more socially anxious drink more in a social drinking situation than do females that are less socially anxious. Male adolescents, in contrast, that show high baseline levels of social behavior drink more in a social context. Thus, females seem to drink alcohol in a social setting to relieve social anxiety whereas socially active males appear to drink socially for social facilitation. We are again using Lac-Z transgenic rats to examine the role of regional ensemble activation in these dramatic sex-specific effects.
ARE THERE LASTING BEHAVIORAL AND COGNITIVE CONSEQUENCES OF ADOLESCENT ALCOHOL EXPOSURE?
We are part of a national research consortium entitled the Neurobiology of Adolescent Drinking in Adulthood (NADIA) that is examining the long-term consequences of repeated adolescent exposure to alcohol using rodent models. We and others in the consortium have shown highly specific lasting neural and behavioral consequences of such exposure. Neural consequences include lasting attenuations in the generation of new neurons (neurogenesis) along with apparent decreases in cholinergic neurons in the basal forebrain. Behavioral alterations we have observed following chronic adolescent alcohol exposure include the maintenance of adolescent-typical behaviors into adulthood, including expression of adolescent-typical social facilitation and an adolescent-typical attenuation in sensitivity to the aversive effects of ethanol. Repeated adolescent alcohol exposure also consistently induces social anxiety and increases in drinking in a social context, with these social anxiety effects being restricted to adult males (not females). This social anxiety was reversed by manipulations of the oxytocin/vasopressin system, suggesting that these peptides may contribute in part to this anxiety. Ongoing work is further exploring the social consequences of adolescent alcohol exposure and the neural consequences of such exposure.
