This application is to study excitatory amino acid inputs and calcium- linked neurotransmitter release during opiate withdrawal. The proposed program of research will examine: 1) spontaneous opiate withdrawal in clinical opiate detoxification studies, and 2) naloxone-precipitated opiate withdrawal in a repeated challenge paradigm. The excitatory amino acid contribution to opiate withdrawal will be studied initially with dextromethorphan, a widely used non-opioid antitussive which inhibits excitatory amino acid neurotransmission in pre-clinical studies, and has shown pilot efficacy for treatment of opiate withdrawal. Based on pre- clinical and pilot human studies, the proposed research will determine the anti-withdrawal efficacy of nimodipine, a centrally-acting calcium channel blocker.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Unknown (K20)
Project #
5K20DA000191-02
Application #
2116098
Study Section
Special Emphasis Panel (SRCD (10))
Project Start
1993-07-01
Project End
1998-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Rosen, M I; Pearsall, H R; Kosten, T R (1998) The effect of lamotrigine on naloxone-precipitated opiate withdrawal. Drug Alcohol Depend 52:173-6
Rosen, M I; Pearsall, H R; Woods, S W et al. (1997) Effects of gamma-hydroxybutyric acid (GHB) in opioid-dependent patients. J Subst Abuse Treat 14:149-54
Rosen, M I; McMahon, T J; Hameedi, F A et al. (1996) Effect of clonidine pretreatment on naloxone-precipitated opiate withdrawal. J Pharmacol Exp Ther 276:1128-35
Rosen, M I; McMahon, T J; Woods, S W et al. (1996) A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal. Eur J Pharmacol 307:251-7
Rosen, M I; McMahon, T J; Margolin, A et al. (1995) Reliability of sequential naloxone challenge tests. Am J Drug Alcohol Abuse 21:453-67
Rosen, M I; Wallace, E A; McMahon, T J et al. (1994) Buprenorphine: duration of blockade of effects of intramuscular hydromorphone. Drug Alcohol Depend 35:141-9