Brent Mancha

Document Type

Honors Project

First Advisor

Dr. Brian Kelley

Degree Award Date

Spring 1999

Keywords

low-level periadolescent nicotine exposure, locomotor properties, adult C57 mice

Disciplines

Animal Sciences | Biology | Laboratory and Basic Science Research

Abstract

As with nicotine, the reinforcing effects of most abused drugs appear to be mediated through dopamine activation. Research, in our lab, has shown that the reinforcing effects of alcohol and cocaine are blunted by nicotine exposure during adolescence. These studies suggest that adolescent exposure to nicotine may permanently alter the reinforcing effects of other drugs due to changes in dopaminergic systems. Behavioral pharmacological methods were used to examine the dopamine-DI and -D2/-D3 receptor systems in adult mice exposed to nicotine (1.0 mg/kg, SC, M-F, b.i.d.) or saline during periadolescence (postnatal days 25-50). Prior to SKF and quinpirole testing, subjects had a 17-day drug-free, time-off period. After acclimation to the testing apparatus (5 days/saline), the locomotor effects (15 min, cm traveled) of SKF (3, 6, 9, and 12 mg/kg, IP) and quinpirole (.02, .04, .08, .16 mg/kg, IP) were measured. SKF and quin. tests were proceeded and followed by saline control tests. After completing the acute dose-response series, mice were given a 15-day drug-free, time-off period; thereafter, mice received saline followed by 5 days of either 12 mg/kg of SKF or .16 mg/kg of quin. An analysis of the acute-SKF raw data revealed that nicotine-mice showed less activity compared to control-mice. An analysis of percent change acute-quin. data revealed that the nicotine-mice showed more activity compared to control-mice (a less pronounced disruption). An analysis of chronic-SKF data showed that nicotine-mice did not recover as rapidly as did the saline-mice. Analyzing the chronic-quin. percent change data showed that nicotine-mice recovered (i.e., developed tolerance) more rapidly then did control-mice. All of these results suggest disruptions in their ability to adapt to acute and repeated D 1 and D2/D3 stimulation.

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