The abuse of prescription medications, which is a growing public health concern, has recently increased sharply, particularly in adolescents. Prescription opioid analgesics are now the third most widely abused illicit substances (after marijuana and amphetamine) in this age group. Adolescence appears to be a period of increased vulnerability to the addictive properties of drugs. Also, there is evidence that the effects of exposure to drugs of abuse such as nicotine during adolescence are long-lasting. Little is known, however, about the effects of opioids in adolescence. Most of what we know about opioid abuse and addiction has been learned from heroin addiction in adult individuals, and from research in adult animals. Information about abuse-related effects of opioids in adolescent animals is lacking partly because several of the procedures commonly used to measure these effects in rodents often require at least several weeks of training, whereas periadolescence in rodents lasts only two weeks. One possible approach is to use species with a longer adolescence, such as primates. However, a less expensive and more practical approach would be to modify lengthy procedures for use in adolescent rodents. The present application is aimed at using rapid procedures to study abuse-related effects of morphine in adolescent mice. Studies under Specific Aim I will examine stimulant-, rewarding-, and sedative effects of morphine in adolescent mice by measuring morphine-induced locomotion, conditioned place preference, and motor impairment, and will compare these effects with those observed in adult animals. Studies under Specific Aim II examine the effects of morphine exposure during adolescence on subsequent sensitivity to the stimulant-, rewarding-, and sedative effects of morphine during adolescence, in comparison with the consequences of such exposure in adults. Based on the results, doses of morphine will be selected that are equi-effective to alter subsequent opioid sensitivity in adolescents and adults. These doses with similar short-term effects in adolescents and adults will be used in studies under Specific Aim III to examine the effects of morphine exposure during adolescence on subsequent opioid sensitivity during adulthood, in comparison with effects of such exposure in adults. Together, these studies will answer the following questions: are adolescent animals 1) more sensitive to abuse-related effects of morphine, 2) more susceptible to the sensitizing effects of morphine exposure, and 3) more likely to show long-term consequences of such exposure? The information resulting from the present studies on age- and exposure dependent differences in opioid sensitivity in mice will provide a basis for future studies of gene-environment interactions such as the role of genetic vulnerability to environmental stress in the sensitivity to opioids. This research will increase our understanding of risk factors for abuse of prescription opioids and will help the development of approaches to prevent and treat this important public health issue.
The abuse of prescription opioid analgesics by adolescents is on the rise. This is particularly worrisome because little is known about the effects of opioids in adolescents, and because adolescence appears to be an especially vulnerable period during which drugs may have different, longer-lasting effects than during adulthood. The studies in this application use adolescent animal models to learn more about the risk factors for abuse of prescription opioid analgesics, which will help to develop approaches to prevent and treat this important public health issue.
|Koek, Wouter (2016) Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice. Psychopharmacology (Berl) 233:2015-24|
|Koek, Wouter (2014) Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss. Psychopharmacology (Berl) 231:1517-29|
|Koek, Wouter; France, Charles P; Javors, Martin A (2012) Morphine-induced motor stimulation, motor incoordination, and hypothermia in adolescent and adult mice. Psychopharmacology (Berl) 219:1027-37|