Document Type

Honors Project

First Advisor

Dr. Brian Kelley

Degree Award Date

Spring 2003

Keywords

Nicotine Exposure, Cocaine Reward, Adult Mice

Disciplines

Biochemistry | Biology | Other Animal Sciences

Abstract

Cigarette smoking by adolescence is a strong predictor of future drug use, abuse, and dependence. While this "gateway drug effect" is assumed to be related to psychosocial factors, data from my laboratory suggests that adolescent nicotine use may permanently disrupt reward systems. Behavioral pharmacological methods known to be indirectly (motor activity, MA) and directly (conditioned-placepreference, CPP) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during periadolescence (postnatal days 25-50). Prior to cocaine testing, subjects had a 30- day drug-free, time-off period. After acclimation to the testing apparatus (5 days/saline), the MA effects (30 min, cm traveled and stereotypy counts) of cocaine (2.5, 5, 10, and 20 mg/kg, IP) were measured daily with 1 injection occurring per day; cocaine tests were preceded and followed by saline control tests. Following the acute dose-response curve, mice received saline followed by 5 days of the 20 mg/kg dose. Thereafter mice underwent CPP testing. A pre-test was performed to determine compartment preference (i.e., no injection, 20-min test). Cocaine (10 mg/kg, IP) was paired with the subjects preferred side. Conditioning sessions (20 min) were conducted for 10 days with the order of drug/saline injections counter-balanced across subjects. A drug-free, post-test occurred on the day following the final conditioning session. A statistically significant, dose-dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's MA effects and a decreased response to cocaine's rewarding effects; this is important because it has been shown that a decrease in the reinforcing effects of abused drugs is a risk factor for abuse and dependence. In summary, this is the first study to demonstrate a dose-response-relationship between adolescent nicotine exposure and changes in drug reward during adulthood.

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