Most research to date using animal models of drug abuse has focused on the effects of psychostimulants on brain neurochemistry and behavior in adult, prenatal, or preweanling animals. There has been little research focusing on the effects of psychostimulants on adolescent rats. However, it is well known that a large number of people who use drugs started as teenagers. Because of this, it is of interest to examine the effects of psychostimulants in this adolescent population in order to determine whether there may be a difference in how this class of drugs effects this age cohort, and on how drug use at this age affects adult susceptibility to addiction. The specific hypothesis of this proposal is that psychostimulants have different effects on the behavior of periadolescent rats than of adult rats, and that exposure to drugs during this critical phase may alter the neurochemical underpinnings of stimulant abuse as an adult. A number of studies have examined the effects of pre-exposure to drugs on later response to cocaine. In all of these studies, both the pre- and post-exposure phases were conducted after the animal had reached adulthood. These studies have shown that pre-exposure to a number of different drugs can influence both the neurochemical and behavioral effects of subsequently administered psychostimulants. Repeated exposure to direct or indirect dopamine agonists in adult rats produces sensitization to the behavioral effects of psychostimulants. Our preliminary data show that, in adult rats, sensitization is evident both during a seven day treatment period, and 10 days after the treatment ends. In contrast, no sensitization is apparent in periadolescent rats treated under the same drug regimen.
The aim of these experiments is to compare the effects of several drugs during the periadolescent phase to during the adult phase. Rats will be treated daily for one week with either cocaine, methylphenidate (ritalin), MDMA (ecstasy) or the appropriate vehicle during the periadolescent or adult phase. Locomotor activity will be tested for one hour daily during this period. Immediately subsequent to this period, or one month later, markers of dopamine and serotonin neurochemistry will be measured. In addition, one month later, the response to cocaine will be tested again on locomotor activity. An understanding of the differential effects of drugs during the periadolescent phase and of how this use impacts drug effects in adults may lead to different treatments for different age groups, as well as a better understanding of how drug use in adolescence may lead to psychostimulant abuse in adulthood.
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