Rodents reared in enriched conditions (EC) during childhood and adolescence have a variety of neurobiological and behavioral differences when compared to rodents reared in standard (SC) or isolated conditions (IC). These neurobiological differences impact numerous behaviors, including the response to drugs of abuse. The neurobiological mechanism for this effect remains unclear. Glutamatergic afferents to the mesocorticolimbic pathway mediate the response to psychostimulants and deficits in glutamate homeostasis are hypothesized to contribute to drug addiction. Differential rearing alters glutamatergic function and therefore our overarching hypothesis is that differential rearing alters glutamate homeostasis. In the proposed experiments, we will examine the effects of differential rearing on astrocyte density and transporters, predominately located on astrocytes, that contribute to glutamate homeostasis. We predict that rearing in an enriched condition, compared to a compared to a standard condition, will augment glutamate homeostasis and increase astrocyte density. Conversely, we predict that rearing in an isolated condition, compared to a standard condition, will impair glutamate homeostasis and decreases astrocyte density.
Specific Aim 1 will determine the relationship between differential rearing, amphetamine exposure, and transporter function. We will include female rats due to literature indicating that differential rearing results in plasticity differences between male and female rats and we predict that protective effects of enrichment will be most robust in female rats.
Specific Aim 2 will determine the effects of differential rearing, amphetamine exposure, and N-acetylcysteine treatment on astrocyte density within the nucleus accumbens. We will measure astrocyte density using immunohistochemistry and predict that enrichment will provide the greatest protection against amphetamine-induced changes in astrocyte density.
Specific Aim 3 will determine if astrocyte density varies as a function of contingent versus non-contingent amphetamine exposure in differentially reared rats. We will administer acute and repeated injections of amphetamine to differentially reared rats and examine GLT-1 and xCT expression using immunoblots and astrocyte density using immunohistochemistry. Completion of these aims will characterize the effects of differential rearing in both male and female rats on glutamate homeostasis, with a specific focus on transporters that predominate on astrocytes. Completion of these aims will strengthen the research environment in the Kansas State University Department of Psychological Sciences and will enable students to participate in all phases of a hypothesis-driven research program.

Public Health Relevance

Rearing in an enriched environment protects against drug abuse while rearing in an isolated environment increases susceptibility to drug abuse. This proposal will explore if differential rearing - induced changes to glutamate receptors and glial cell density contribute to the differences in drug abuse vulnerability. The findings of this research are intended to advance the understanding of the basic neural mechanisms mediating the effects of the early environment on later drug use.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Academic Research Enhancement Awards (AREA) (R15)
Project #
Application #
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Grant, Steven J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Kansas State University
Schools of Arts and Sciences
United States
Zip Code
Garcia, Erik J; Jorgensen, Emily T; Sprick, Lukas S et al. (2017) Voluntary ethanol consumption changes anticipatory ultrasonic vocalizations but not novelty response. Behav Brain Res 320:186-194
Garcia, Erik J; Haddon, Tara N; Saucier, Donald A et al. (2017) Differential housing and novelty response: Protection and risk from locomotor sensitization. Pharmacol Biochem Behav 154:20-30
Garcia, Erik J; Cain, Mary E (2016) Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats. Psychopharmacology (Berl) 233:625-37
Arndt, D L; Johns, K C; Dietz, Z K et al. (2015) Environmental condition alters amphetamine self-administration: role of the MGluR? receptor and schedule of reinforcement. Psychopharmacology (Berl) 232:3741-52
Arndt, David L; Arnold, Jennifer C; Cain, Mary E (2014) The effects of mGluR2/3 activation on acute and repeated amphetamine-induced locomotor activity in differentially reared male rats. Exp Clin Psychopharmacol 22:257-65