The objectives of the present proposal are to combine and integrate behavioral and biochemical techniques (i) to characterize further the serotonergic-glutamatergic interaction in drug-induced stimulus control by indoleamine and phenethylamine hallucinogens and (ii) to determine the molecular mechanisms involved in this interaction. Thus, behavioral results using drug discrimination, which is widely believed to have significant subjective correlates in humans, will be correlated and compared with various biochemical measures of efficacy such as the in vivo release of neurotransmitter and reversible molecular modifications of the NMDA receptor. This study will utilize techniques of microinjection and microdialysis to create and study conditions at the cellular level present during administration of hallucinogen. The study will also utilize drug discrimination as a way to correlate said conditions with behavior in rats. Hallucinogens are a significant health care problem in adolescents and young adults, with the use of these drugs surpassing that of cocaine. Furthermore, the ability of some hallucinogens to mimic human psychosis suggests that an elucidation of the mechanisms of action of hallucinogenic drugs may contribute to an understanding of schizophrenia and other psychotic disorders.

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 #
1F30DA014238-01
Application #
6339715
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2001-03-21
Project End
Budget Start
2001-03-21
Budget End
2002-03-20
Support Year
1
Fiscal Year
2001
Total Cost
$27,358
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
Winter, J C; Eckler, J R; Rice, K C et al. (2005) Serotonergic/glutamatergic interactions: potentiation of phencyclidine-induced stimulus control by citalopram. Pharmacol Biochem Behav 81:694-700
Winter, J C; Eckler, J R; Rabin, R A (2004) Serotonergic/glutamatergic interactions: the effects of mGlu2/3 receptor ligands in rats trained with LSD and PCP as discriminative stimuli. Psychopharmacology (Berl) 172:233-40
Muschamp, John W; Regina, Meredith J; Hull, Elaine M et al. (2004) Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res 1023:134-40
Regina, Meredith J; Bucelli, Robert C; Winter, Jerrold C et al. (2004) Cellular mechanisms of serotonin 5-HT2A receptor-mediated cGMP formation: the essential role of glutamate. Brain Res 1003:168-75
Regina, Meredith J; Winter, Jerrold C; Rabin, Richard A (2003) Characterization of a novel effect of serotonin 5-HT1A and 5-HT2A receptors: increasing cGMP levels in rat frontal cortex. Neuropharmacology 45:1041-9
Winter, J C; Eckler, J R; Doat, M M et al. (2002) The effects of acute and subchronic treatment with fluoxetine and citalopram on stimulus control by DOM. Pharmacol Biochem Behav 74:95-101