Hallucinogens, including the club drugs phencyclidine (PCP), ketamine, 3,4-methylenedioxy-N-methamphetamine (MDMA), and lysergic acid diethylamide (LSD), continue to be subject to widespread abuse by adolescents and young adults in this country. Data from the most recent National Survey on Drug Use and Health (SAMHSA, 2003) indicate that fully 45% of those using these drugs for the first time were under the age of 18. Among this class of drugs, the study of LSD and PCP offer perhaps a unique opportunity to elucidate and contribute to the understanding of psychosis as well as ameliorating the burdens of illicit and abusive drug use. Drug-induced stimulus control is a powerful tool for the study of behaviorally active drugs in intact animals that has identified clear distinctions in the mechanisms of action of non-competitive antagonists at the NMDA subtype of glutamate receptors, such as PCP, and serotonergic agents like LSD. However, it has also been observed that non-competitive antagonists of the NMDA receptor subtype potentiate the stimulus effects of both the phenethylamine hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and LSD. Therefore, most recently, it has been hypothesized that glutamate release may be a final common pathway for the actions both of serotonergic and glutamatergic hallucinogens. This hypothesis draws support from behavioral studies using drugs that modify glutamate release in vivo that also have discriminative effects. However, a direct relationship between glutamate release and LSD-induced behavior is lacking. The objectives of the present proposal are to use a combination of behavioral and biochemical approaches to: [i] clarify the role of cortical glutamate release in the stimulus effects of LSD, and [ii] determine the effect of drugs that modulate LSD-induced behavior on extra cellular glutamate levels in the medial prefrontal cortex ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30DA021048-01A1
Application #
7221020
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2007-03-05
Project End
2009-03-04
Budget Start
2007-03-05
Budget End
2008-03-04
Support Year
1
Fiscal Year
2007
Total Cost
$29,904
Indirect Cost
Name
State University of New York at Buffalo
Department
Pharmacology
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260