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 (NAcc) 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. It is not clear how the environment determines the trajectory of drug abuse among adolescents. The current basic research will determine the behavioral and neurobiological consequences of raising adolescent rats in different environments. Results obtained thus far indicate that environmental enrichment protects against drug abuse vulnerability.
It is not clear how the environment determines the trajectory of drug abuse among adolescents. The current basic research will determine the behavioral and neurobiological consequences of raising adolescent rats in different environments. Results obtained thus far indicate that environmental enrichment protects against drug abuse vulnerability.
|Sunsay, Ceyhun; Rebec, George V (2014) Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens core during Pavlovian conditioning. Behav Neurosci 128:579-87|
|Hofford, Rebecca S; Darna, Mahesh; Wilmouth, Carrie E et al. (2014) Environmental enrichment reduces methamphetamine cue-induced reinstatement but does not alter methamphetamine reward or VMAT2 function. Behav Brain Res 270:151-8|
|Nakhnikian, Alexander; Rebec, George V; Grasse, Leslie M et al. (2014) Behavior modulates effective connectivity between cortex and striatum. PLoS One 9:e89443|
|Yates, Justin R; Beckmann, Joshua S; Meyer, Andrew C et al. (2013) Concurrent choice for social interaction and amphetamine using conditioned place preference in rats: effects of age and housing condition. Drug Alcohol Depend 129:240-6|
|Zhu, Jun; Bardo, Michael T; Dwoskin, Linda P (2013) Distinct effects of enriched environment on dopamine clearance in nucleus accumbens shell and core following systemic nicotine administration. Synapse 67:57-67|
|Fischer, Kathryn D; Houston, Alexander C W; Rebec, George V (2013) Role of the major glutamate transporter GLT1 in nucleus accumbens core versus shell in cue-induced cocaine-seeking behavior. J Neurosci 33:9319-27|
|Bardo, M T; Neisewander, J L; Kelly, T H (2013) Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharmacol Rev 65:255-90|
|Beckmann, Joshua S; Bardo, Michael T (2012) Environmental enrichment reduces attribution of incentive salience to a food-associated stimulus. Behav Brain Res 226:331-4|
|Fischer-Smith, K D; Houston, A C W; Rebec, G V (2012) Differential effects of cocaine access and withdrawal on glutamate type 1 transporter expression in rat nucleus accumbens core and shell. Neuroscience 210:333-9|
|Perry, Jennifer L; Joseph, Jane E; Jiang, Yang et al. (2011) Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions. Brain Res Rev 65:124-49|
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