This project aims to elucidate the mechanisms by which selective serotonin reuptake inhibitors (SSRI's), alter DOM induced stimulus control. SSRI's, as a class, are known to interact with CYP 450 isoforms. In order to study the pharmacodynamic mechanism of potentiation, GC-MS will be used to identify SSRI's that do not alter DOM brain levels. Drug discrimination studies will indicate if SSRI's can both mimic and potentiate the stimulus properties of DOM. The stimulus effects of DOM are believed to be mediated by 5-HT2A and modulated by 5-HT2C serotonergic receptors. The affinity of SSRI's for these receptors will be elucidated by receptor binding studies. SSRI's will be injected into rat cerebral ventricles to determine if a metabolite or the parent SSRI is altering the stimulus properties of DOM. Affinity of DOM for the 5-HT transporter as well as the effect of SSRI's on uptake of DOM in rat brain synaptosomes will be assessed. The inhibition of DOM uptake by the 5-HT transporter in the presence of SSR1's would indicate that the observed potentiation is a result of this inhibition and not a direct effect of SSRI's at the 5-HT2A and 5-HT2C receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA013920-02
Application #
6453550
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2001-10-01
Project End
Budget Start
2001-10-01
Budget End
2002-09-30
Support Year
2
Fiscal Year
2001
Total Cost
$25,097
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
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Eckler, J R; Reissig, C J; Rabin, R A et al. (2004) A 5-HT(2C) receptor-mediated interaction between 2,5-dimethoxy-4-methylamphetamine and citalopram in the rat. Pharmacol Biochem Behav 79:25-30
Eckler, J R; Rabin, R A; Winter, J C (2003) Nefazodone in the rat: mimicry and antagonism of [-]-DOM-induced stimulus control. Pharmacol Biochem Behav 75:405-10
Eckler, J R; Chang-Fong, J; Rabin, R A et al. (2003) Behavioral characterization of 2-O-desmethyl and 5-O-desmethyl metabolites of the phenylethylamine hallucinogen DOM. Pharmacol Biochem Behav 75:845-52
Eckler, J R; Doat, M M; Rabin, R A et al. (2002) Potentiation of DOM-induced stimulus control by fluoxetine and citalopram: role of pharmacokinetics. Life Sci 71:1341-7
Eckler, J R; Greizerstein, H; Rabin, R A et al. (2001) A sensitive method for determining levels of [-]-2,5,-dimethoxy-4-methylamphetamine in the brain tissue. J Pharmacol Toxicol Methods 46:37-43