Drug self-administration in rodents is a useful technique to examine the mechanisms and potential treatment of stimulant abuse. Previous research has shown that stimulant self-administration is greater in rats that are highly active in a novel environment (high responders) compared to rats that are relatively inactive (low responders). In addition, stimulant self-administration is greater in rats raised in an isolated environment compared to rats raised in an enriched environment. The experiments proposed in the present application will determine if rats that are prone to self-administer amphetamine, due to genetic or environmental factors, share a common neural profile of an overactive arousal system. The overall mechanistic framework for the proposed set of experiments is based on the role of the central nucleus of the amygdala (ACe) in regulating arousal due to its extensive cortical and subcortical projections. We hypothesize that the ACe is more active in high responder rats compared to low responder rats and in rats reared in an isolated condition compared to an enriched condition. The effects of ibotenic acid lesions of the ACe on subsequent amphetamine self-administration will be measured. In addition, the amount of c-Fos labeling will be measured in the ACe to determine if the ACe has greater activity in those rats prone to self-administer amphetamine. The findings from these experiments are intended to advance the understanding of vulnerability for stimulant abuse, and will potentially lead to better prevention and treatment interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA016013-01
Application #
6583912
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Hoffman, Allison
Project Start
2002-10-01
Project End
2004-07-31
Budget Start
2002-10-01
Budget End
2003-09-30
Support Year
1
Fiscal Year
2002
Total Cost
$39,831
Indirect Cost
Name
University of Kentucky
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Cain, Mary E; Denehy, Emily D; Bardo, Michael T (2008) Individual differences in amphetamine self-administration: the role of the central nucleus of the amygdala. Neuropsychopharmacology 33:1149-61
Cain, Mary E; Dotson, William F; Bardo, Michael T (2006) Individual differences in the effect of novel environmental stimuli prior to amphetamine self-administration in rats (Rattus norvegicus). Exp Clin Psychopharmacol 14:389-401
Cain, Mary E; Green, Thomas A; Bardo, Michael T (2006) Environmental enrichment decreases responding for visual novelty. Behav Processes 73:360-6
Bardo, M T; Cain, M E; Bylica, K E (2006) Effect of amphetamine on response inhibition in rats showing high or low response to novelty. Pharmacol Biochem Behav 85:98-104
Cain, Mary E; Saucier, Donald A; Bardo, Michael T (2005) Novelty seeking and drug use: contribution of an animal model. Exp Clin Psychopharmacol 13:367-75
Cain, Mary E; Smith, C Matthew; Bardo, Michael T (2004) The effect of novelty on amphetamine self-administration in rats classified as high and low responders. Psychopharmacology (Berl) 176:129-38
Green, Thomas A; Cain, Mary E; Thompson, Michael et al. (2003) Environmental enrichment decreases nicotine-induced hyperactivity in rats. Psychopharmacology (Berl) 170:235-41