Abstract

This project is designed to use positron emission tomography (PET) to investigate the functional linkage of neurotransmitter systems. Specifically, it will focus on the interactions of dopamine and serotonin since both systems have been implicated in schizophrenia, depression and affective disorders. The applicants will use PET to quantify the responsiveness of dopaminergic and serotonergic systems to specific pharmacologic challenges. These studies will use C-11 raclopride (RAC), a D2/D3 receptor antagonist, to image postsynaptic dopamine receptors and a new ligand, C-11 SR46349B, a serotonin (5-HT2) antagonist. By observing dose response and time course of events, the ability of PET to quantify pharmacologic activity will be validated by assessing the following: (1) the sensitivity of the response at different challenge doses, (2) the reproducibility of response, (3) the stability of the baseline measurement and (4) the time course of response to the challenge. Also the effect of anesthesia on these interactions will be investigated. Finally, findings in non-human primates will be confirmed by using in vivo microdialysis in freely moving rats to study changes in endogenous neurotransmitter levels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049165-07
Application #
2756849
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1992-08-01
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973

  Publications

Marsteller, Douglas A; Gerasimov, Madina R; Schiffer, Wynne K et al. (2002) Acute handling stress modulates methylphenidate-induced catecholamine overflow in the medial prefrontal cortex. Neuropsychopharmacology 27:163-70
Gerasimov, M R; Schiffer, W K; Gardner, E L et al. (2001) GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine. Eur J Pharmacol 414:205-9
Schiffer, W K; Gerasimov, M R; Marsteller, D A et al. (2001) Topiramate selectively attenuates nicotine-induced increases in monoamine release. Synapse 42:196-8
Schiffer, W K; Gerasimov, M; Hofmann, L et al. (2001) Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission. Neuropsychopharmacology 25:704-12
Gerasimov, M R; Schiffer, W K; Brodie, J D et al. (2000) gamma-aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine. Eur J Pharmacol 395:129-35
Gerasimov, M R; Franceschi, M; Volkow, N D et al. (2000) Comparison between intraperitoneal and oral methylphenidate administration: A microdialysis and locomotor activity study. J Pharmacol Exp Ther 295:51-7
Gerasimov, M R; Franceschi, M; Volkow, N D et al. (2000) Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor. Synapse 38:432-7
Schiffer, W K; Gerasimov, M R; Bermel, R A et al. (2000) Stereoselective inhibition of dopaminergic activity by gamma vinyl-GABA following a nicotine or cocaine challenge: a PET/microdialysis study. Life Sci 66:PL169-73
Dewey, S L; Brodie, J D; Gerasimov, M et al. (1999) A pharmacologic strategy for the treatment of nicotine addiction. Synapse 31:76-86
Gerasimov, M R; Dewey, S L (1999) Gamma-vinyl gamma-aminobutyric acid attenuates the synergistic elevations of nucleus accumbens dopamine produced by a cocaine/heroin (speedball) challenge. Eur J Pharmacol 380:1-4

Showing the most recent 10 out of 26 publications