In the proposed research we plan to continue experiments that will elucidate the neurobehavioral bases of the effects of the CNS stimulants, i.e., cocaine and d-amphetamine, and opioids on rewarding brain stimulation. Our previous work has indicated that all drugs that increase the sensitivity of animals to this stimulation are either abuse substances or have the potential for abuse. The opioids that we will study are morphine, heroin, the mixed agonist-antagonist pentazocine, as well as the kappa agonists ethylketocyclazocine and U-50,488. We will study the effects of both opioid and dopaminergic blocking agents on the effect of these compounds. We will compare their effects in animals with electrodes in various brain sites. Further we will attempt to determine the mechanisms involved in the potentiation of the reward threshold lowering effect with the mixed agonist-antagonists by the antihistaminic tripelennamine (this combination has the street name of """"""""T's and Blues""""""""). By means of the 2-deoxyglucose method we will determine the effects of some of the above drugs on local cerebral glucose utilization during rewarding brain stimulation. We also will use 6-hydroxydopamine as a tool to deplete specific dopaminergic nuclei in order to further elaborate the relationship between dopaminergic and opiate systems in the mediation of the observed effect of opioids and CNS stimulants. Using brain-stimulation escape as a method for the study of the analgesic effects of drugs we will attempt to determine whether or not the observed potentiation of the analgesic action of morphine by amphetamine is unique for amphetamine or will other catecholaminergic agents will also potentiate the analgesic effect of morphine. Of practical importance is whether or not d-amphetamine would potentiate the analgesic response of a drug with less analgesic efficacy than morphine. By using the 2-deoxyglucose method we will compare the effects of nociceptive stimulation to the mesencephalic reticular formation after morphine, naloxone, and d-amphetamine plus morphine in combination. It is through these experiments that we hope to contribute to our understanding of why abuse substances are rewarding.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002326-11
Application #
3207262
Study Section
Special Emphasis Panel (DABA)
Project Start
1979-12-01
Project End
1990-12-31
Budget Start
1989-12-01
Budget End
1990-12-31
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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
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
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
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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