This research is directed toward furthering our understanding of the neuronal bases of the reinforcing effects of abused substances with special emphasis on the opiates and the psychomotor stimulants, e.g. cocaine. Included will be complementary studies of the analgesic effects of opiate drugs and the manner that non-opioid systems may contribute to these effects. The major neurobehavioral model that we use for the study of the reinforcing effects of abuse substances is brain-stimulation reward. We have consistently found that all drugs that lower the threshold for rewarding electrical stimulation to the brain, are abused, have potential for abuse as confirmed by independent criteria. or in a few cases have effects on non-reward systems that would preclude use. Using the brain-stimulation reward model we plan a series of experiments to determine the extent that identical neuronal systems are involved in the mediation of the threshold lowering effects of the opiate drugs and the psychomotor stimulants. The 2-(14C)deoxyglucose method of determining local cerebral glucose utilization (LCGU). use of the neurotoxin 6-OHDA, and the interaction of the effects of dopamine and opiate antagonists with drugs that lower the threshold for rewarding brain simulation will be studied. In order to determine if there are differences in neuronal systems involved in the reinforcing and the analgesic effects of opiates. morphine's effects on LCGU will be compared in animals working to receive rewarding brain stimulation, or to escape from nociceptive brain stimulation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
2K05DA000099-06
Application #
3075422
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1983-12-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Kornetsky, Conan; Knapp, Clifford M; Tozier, Lisa et al. (2010) Medial forebrain stimulation enhances intracranial nociception and attenuates morphine analgesia suggesting the existence of an endogenous opioid antagonist. Pharmacol Biochem Behav 95:273-7
Knapp, Clifford M; Tozier, Lisa; Pak, Arlene et al. (2009) Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats. Pharmacol Biochem Behav 92:474-9
Vassoler, Fair M; Schmidt, Heath D; Gerard, Mary E et al. (2008) Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats. J Neurosci 28:8735-9
Knapp, Clifford M; Mercado, Melissa; Markley, Tara Lynn et al. (2007) Zonisamide decreases ethanol intake in rats and mice. Pharmacol Biochem Behav 87:65-72
Crosby, Steven J; Knapp, Clifford M; Kornetsky, Conan (2006) Nociceptive threshold and analgesic response to morphine in aged and young adult rats as determined by thermal radiation and intracerebral electrical stimulation. Pharmacol Biochem Behav 84:148-57
Jha, Shivkumar H; Knapp, Clifford M; Kornetsky, Conan (2004) Effects of morphine on brain-stimulation reward thresholds in young and aged rats. Pharmacol Biochem Behav 79:483-90
Knapp, Clifford M; Jha, Shivkumar H; Kornetsky, Conan (2004) Increased sensitization to morphine-induced oral stereotypy in aged rats. Pharmacol Biochem Behav 79:491-7
Gill, Brian M; Knapp, Clifford M; Kornetsky, Conan (2004) The effects of cocaine on the rate independent brain stimulation reward threshold in the mouse. Pharmacol Biochem Behav 79:165-70
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

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