Projects and Grants per year
Grants and Contracts Details
Description
There has been considerable emphasis on research aimed at determining the genetic factors
responsible for phenotypic expression of increased drug abuse vulnerability. Identification of the multiple
genetic factors that determine vulnerability is critically important and currently feasible with modern molecular
technology. However, significant efforts also need to be directed at understanding the impact of intervening
environmental factors that modify the trajectory of an individual's genetic vulnerability. In this competitive
renewal application, we will investigate the effects of environmental enrichment during development on drug
abuse vulnerability during adulthood.
Evidence to date indicates that repeated exposure to novel stimuli (i.e., the "enriched" condition; EC)
during the periadolescent period produces profound changes in response to novelty and response to drugs of
abuse later in life. We have found that EC rats display less motivation for sucrose and for visual novelty, as
well as less impulsivity for obtaining sucrose reward, compared to rats raised in an "impoverished" condition
(IC). EC rats also show a reduction in amphetamine self-administration compared to IC rats when tested with
low unit doses. These enrichment-induced behavioral changes are accompanied by a reduction in uptake and
metabolism of dopamine (DA) in presynaptic terminals in medial prefrontal cortex (mPFC), a brain region
known to be involved in both drug reward and behavioral inhibition, perhaps via a modulatory influence on DA
activity in the nucleus accumbens (MAcc) and other related components of the motivational circuitry.
The overall working hypothesis of this application is that exposure to novel environmental stimulation
during development protects against stimulant abuse because there is a decrease in the incentive value of
positive reinforcers and a concomitant increase in behavioral inhibition, with each of these processes being
associated with changes in corticolimbic activity. The specific aims are to determine if environmental
enrichment:
1. protects against escalating stimulant intake across long access sessions;
2. alters behavioral inhibition following stimulant exposure;
3. alters patterns of neuronal activity in corticolimbic and striatal regions involved in reward and inhibition;
and
4. alters monoamine transporter function in corticolimbic and striatal regions involved in
reward and inhibition.
Status | Finished |
---|---|
Effective start/end date | 3/1/00 → 6/30/16 |
Funding
- National Institute on Drug Abuse: $1,717,577.00
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Projects
- 1 Finished
-
Novelty, Dopamine and Response to Amphetamine
Dwoskin, L. (PI)
National Institute on Drug Abuse
3/1/00 → 6/30/16
Project: Research project