In recent years a Major thrust in the study of the characteristics of the drug abuser has focused on vulnerability, the possible role that genetics play in this vulnerability, and the molecular underpinnings of the mechanisms of use and relapse into drug use. Intrinsic to the understanding of these problems is the understanding of the mechanisms involved in the action of the abused substances on the brain reward system(s). However, for the most part, researchers have made use of the rat as the animal of choice for study, while most of the experiments on genetic differences make use of mouse as the experimental animal. In trying to investigate the behavior of these genetic mutations investigators have relied mostly on simple unconditioned behavior. The proposed research is designed to adapt for the mouse techniques for measuring the changes in brain-stimulation reward (BSR) that have been successfully used in the rat. The procedures are 1) a discrete trial, rate independent, psychophysical method for measuring the BSR threshold and 2) a parallel procedure that measures the ability of the animal to attend to a stimulus by measuring the detection of non-rewarding stimulation from the same brain site. In addition to measuring the stimulation thresholds, latency of response is also measured. Thus the techniques allow for the determination of not only changes in the reward system but also whether these changes are confounded by motor and attention factors. The proposed experiments will explore differences in response to morphine and cocaine in CB57/B6 and D, and DAT deficient mutant mice. Successful development of these procedures in mice will allow a more specific understanding of the nature of specific phenotypes that may have relationships to the human condition.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA014184-03
Application #
6634367
Study Section
Special Emphasis Panel (ZDA1-KXA-N (08))
Program Officer
Volman, Susan
Project Start
2001-04-15
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2005-03-31
Support Year
3
Fiscal Year
2003
Total Cost
$163,000
Indirect Cost
Name
Boston University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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