Abstract

The thesis of this research is that the opioid drugs as well as many other drugs of abuse are used for their pleasurable effects and that a relevant animal model is the action of these drugs on the brain pathways that support intracranial self-stimulation. Many drugs of abuse will cause a lowering of the reinforcement threshold for self-stimulation. We propose that these effects reflect a functional increase in the sensitivity of the underlying neural systems, which may be directly related to the hedonic subjective effects of these compounds, and hence their abuse potential. The principal technique that we will use is the measurement of the threshold for intracranial self-stimulation in the rat. Various areas of the brain that support self-stimulation (rewarding) as well as those areas that are negatively reinforcing (aversive) will be investigated. In addition to the reinforcement threshold for self-stimulation we will study the effects of these drugs on the detection threshold for stimulation to both rewarding and aversive sites in the brain. The compounds to be studied will include the opiate agonist, partial agonist and antagonist as well as amphetamine, cocaine, phencyclidine and a number of putative endogenous peptides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002326-06
Application #
3207258
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1979-12-01
Project End
1985-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Knapp, Clifford M; Printseva, Bella; Cottam, Nicole et al. (2002) Effects of cue exposure on brain glucose utilization 8 days after repeated cocaine administration. Brain Res 950:119-26
Knapp, C M; Foye, M M; Cottam, N et al. (2001) Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration. Pharmacol Biochem Behav 68:797-803
Knapp, C M; Lee, K; Foye, M et al. (2001) Additive effects of intra-accumbens infusion of the cAMP-specific phosphodiesterase inhibitor, rolipram and cocaine on brain stimulation reward. Life Sci 69:1673-82
Kraus, M A; Kornetsky, C (2000) Cue-induced changes in basal local cerebral glucose utilization 13 days after morphine sensitization in the Fischer 344 rat: relevance for drug craving. Brain Res 865:194-201
Wennemer, H K; Kornetsky, C (1999) Fluoxetine blocks expression but not development of sensitization to morphine-induced oral stereotypy in rats. Psychopharmacology (Berl) 146:19-23
Kushner, S A; Dewey, S L; Kornetsky, C (1999) The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats. J Pharmacol Exp Ther 290:797-802
Knapp, C M; Foye, M M; Ciraulo, D A et al. (1999) The type IV phosphodiesterase inhibitors, Ro 20-1724 and rolipram, block the initiation of cocaine self-administration. Pharmacol Biochem Behav 62:151-8
Duvauchelle, C L; Fleming, S M; Kornetsky, C (1998) Prefrontal cortex infusions of SCH 23390 cause immediate and delayed effects on ventral tegmental area stimulation reward. Brain Res 811:57-62
Duvauchelle, C L; Sapoznik, T; Kornetsky, C (1998) The synergistic effects of combining cocaine and heroin (""speedball"") using a progressive-ratio schedule of drug reinforcement. Pharmacol Biochem Behav 61:297-302
Lee, K; Kornetsky, C (1998) Acute and chronic fluoxetine treatment decreases the sensitivity of rats to rewarding brain stimulation. Pharmacol Biochem Behav 60:539-44

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