Behavioral Effects of Dissociatives in Adolescents: Comparison with Adults

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DESCRIPTION (provided by applicant): The broad goal of this research is to better understand the behavioral effects of dissociatives, with a particular focus on their effects in adolescents. Dissociatives, including phencyclidine (PCP) and ketamine were originally developed as anesthetics, but are being increasingly used at subanesthetic doses for both clinical and non-clinical purposes. These drugs have been used in human clinical studies and preclinical animal models to better understand and treat two major psychiatric disorders, schizophrenia and major depression. In addition, evidence indicates that subanesthetic doses of dissociatives are useful in the treatment of pain. Dissociatives are also an important class of abused drugs, often classified as 'club drugs'. Dissociatives are of special interest and importance to adolescents. These drugs are often used by teens in dance club or "rave" settings. Survey research shows increased use of dissociatives by teens in recent years, as well as decreased age for initiation of use. This is true for both PCP and ketamine, as well as the over-the-counter cough suppressant, dextromethorphan. Despite all of this, no published research has systematically examined differences between adolescents and adults in the behavioral effects of dissociatives. The current project will compare the behavioral effects of dissociatives (including ketamine, PCP and dextromethorphan) in adolescent and adult laboratory rats. In addition to examining differences in the acute response to these drugs, the studies will also explore differences following repeated administration, and in particular, a phenomenon known as behavioral sensitization. Sensitization is an increase in an effect of a drug following repeated use, and is thought to be important to the development of addiction. The following specific aims will be examined: 1) to compare the acute behavioral effects of dissociatives in adolescent and adult rats; 2) to compare the development of sensitization to dissociatives in adolescent and adult rats; 3) to assess the role of glutamate release in the behavioral effects of dissociatives in adolescent and adult rats; and 4) to compare the plasma concentrations of dissociatives in adolescent and adult rats. Together, the research will lead to a better understanding of the effects of dissociatives in adolescents and adults, and may lead to better treatments for schizophrenia, depression, pain and drug abuse.