Graduation Year

2005

Document Type

Thesis

Degree

M.A.

Degree Granting Department

Psychology

Major Professor

Cheryl L. Kirstein, Ph.D.

Committee Member

Toru Shimizu, Ph.D.

Committee Member

James Willott, PhD.

Committee Member

Mark Goldman, Ph.D.

Keywords

ontogeny, adolescent rat, nucleus accumbens, addiction, quantitiative in vivo microdialysis

Abstract

In humans, adolescent exposure to illicit drugs predicts the onset of adult drug abuse and suggests that early drug use potentiates adolescent vulnerability to drug addiction. In experiment 1, it was hypothesized that adolescent rats would show a CPP for a low cocaine dose if in fact adolescents are more vulnerable to cocaine's rewarding effects. Place preferences were measured in early adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them to environmental cues in a 2-chamber place conditioning apparatus. Significant cocaine preferences were found for all ages at the high dose. Interestingly, PND 35's were the only age group to have a CPP at the low dose suggesting that PND 35 rats are more sensitive than late adolescent and young adult rats to cocaine's rewarding effects. In Experiment 2, it was hypothesized that age-related differences in cocaine CPP may be mediated by differences in the mesolimbic dopaminergic (DA) system throughout development. Extracellular DA levels in the nucleus accumbens septi (NAcc) of early adolescent, late adolescent and adult rats were measured via quantitative microdialysis. PND 35, PND 45 and PND 60 rats were injected daily with either 5 mg/kg/ip or saline for 4 days, surgically implanted with a microdialysis probe aimed at the NAcc. Rats were perfused with either 0, 1, 10 or 40 nM DA and the extracellular DA concentration was measured. Our results show that adolescents differ from adults in basal DA with PND 35 rats having low basal DA (0.4 nM), PND 45 rats having high basal DA (1.8 nM) and PND 60 rats having intermediate basal DA (1.3 nM). PND 45 cocaine treated rats showed a 58% decrease in basal DA. All cocaine treated rats, regardless of age, showed a significant increase in DA over baseline in response to a cocaine challenge. Additionally, there were age-related differences in the extraction fraction (Ed), an indirect measure of DA reuptake, with PND 45 and PND 60's showing a decrease in basal Ed, an effect absent in PND 35's. Together these findings suggest that there are substantial ontogenetic differences in extracellular DA and DA reuptake and that these differences may provide an explanation for adolescent vulnerability to addiction. Future research should investigate DA supply and degradation processes in naïve and cocaine treated adolescent rats and vulnerability to addiction.

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