The major long-term objective of this scientist award is to conduct research comparing young and old rat's response to opiates and cocaine. Preliminary data has suggested major differences in reward mechanisms between young and old rats. As the population grows older the number of elderly individuals with drug dependence may sharply increase; the issue, however, of drug abuse in aging has, for the most part, been ignored. There is considerable evidence that with aging there are alterations in the brain systems implicated in the mediation of the hedonic effects of abused substances. A major aspect of the proposed research will examine the functional consequences of these alterations using a number of animal models of the rewarding effects of abused substances. Specifically the abuse substances studied will be morphine, heroin and cocaine as well as specific substances that alter the relevant neurotransmitter systems that are believed involved in the rewarding effects of these abused substances. The experimental animal will be the rat and the specific models used will be drug self-administration, conditioned place preference, and brain stimulation reward. In addition the specific dopamine (DA) agonist GBR 12009 will be investigated. DA within the nucleus accumbens will be measured using in vivo micro-dialysis in aged and young animals following the administration of morphine, GBR 12909 and BSR, alone and in combination. Another area or research will to experimentally investigate basal changes in the brain that are precipitated by the presentation of environmental cues that previously had been associated with alcohol during drinking bouts in rats this model will make use of the quantitative 2-deoxy-glucose ((2-DG) Auto radiographic method of determining local cerebral metabolic rate of glucose metabolism. In addition to the research experiments it is proposed to write a historical review of the behavioral methods that have been used in the study of abused substances.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA000099-25
Application #
7340453
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wetherington, Cora Lee
Project Start
1993-12-10
Project End
2008-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
25
Fiscal Year
2008
Total Cost
$120,820
Indirect Cost
Name
Boston University
Department
Psychiatry
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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