Abstract

The proposed project addresses the ability of competitive N-methyl-D-aspartate (NMDA) receptor antagonists to affect responding conditioned with drugs of abuse (morphine, cocaine). It is proposed to study in rats the influence of site-selective NMDA antagonists on: (1) the drug-conditioned activation of locomotor activity; (2) the facilitation of intracranial self-stimulation induced by conditioned stimuli associated with abused drugs or rewarding electrical stimulation; (3) the responding maintained by conditioned reinforcers using intravenous drug self-administration procedures. The NMDA antagonists are to be administered systemically and also centrally into the nucleus accumbens septi through chronically implanted cannuli. The results will clarify the role of the glutamatergic excitatory system, especially its projections to the nucleus accumbens, in mediating the expression of responses conditioned through exposure to drugs of abuse. Secondarily, considering the role conditioned drug effects may have for relapse to, and maintenance of, drug seeking, the results may also provide important directions for the development of medications for the treatment of drug abuse.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW000714-03
Application #
2736204
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Dravolina, Olga A; Zakharova, Elena S; Shekunova, Elena V et al. (2007) mGlu1 receptor blockade attenuates cue- and nicotine-induced reinstatement of extinguished nicotine self-administration behavior in rats. Neuropharmacology 52:263-9
Dravolina, Olga A; Danysz, Wojciech; Bespalov, Anton Y (2006) Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats. Psychopharmacology (Berl) 187:397-404
Bespalov, Anton Y; Dravolina, Olga A; Sukhanov, Ilya et al. (2005) Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats. Neuropharmacology 49 Suppl 1:167-78
Belozertseva, Irina V; Sukhotina, Irina A; Vossen, Jo M H et al. (2004) Facilitation of aggressive and sexual behaviors by saccharin deprivation in rats. Physiol Behav 80:531-9
Zakharova, E; Malyshkin, A; Kashkin, V et al. (2004) The NMDA receptor channel blocker memantine and opioid receptor antagonist naltrexone inhibit the saccharin deprivation effect in rats. Behav Pharmacol 15:273-8
Sukhotina, Irina A; Malyshkin, Andrey A; Markou, Athina et al. (2003) Lack of depression-like effects of saccharin deprivation in rats: forced swim test, differential reinforcement of low rates and intracranial self-stimulation procedures. Behav Neurosci 117:970-7
Popik, P; Wrobel, M; Rygula, R et al. (2003) Effects of memantine, an NMDA receptor antagonist, on place preference conditioned with drug and nondrug reinforcers in mice. Behav Pharmacol 14:237-44
Bespalov, A Y; Medvedev, I O; Sukhotina, I A et al. (2001) Effects of the NMDA receptor antagonist, D-CPPene, on sensitization to the operant decrement produced by naloxone in morphine-treated rats. Behav Pharmacol 12:135-42
Blokhina, E A; Sukhotina, I A; Bespalov, A Y (2000) Pretreatment with morphine potentiates naloxone-conditioned place aversion in mice: effects of NMDA receptor antagonists. Eur J Pharmacol 406:227-32
Neznanova, O N; Blokhina, E A; Sukhotina, I A et al. (2000) Motor impairment produced by ethanol and site-selective NMDA receptor antagonists in mice: tolerance and cross-tolerance. Alcohol 20:31-6

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