Mice will be obtained from the Institute of Behavioral Genetics, Boulder, Colorado. The mice have been bred for high (H1,H2) or low (L1,L2) motor activity and there are two groups of randomly bred control mice (C1,C2). The high activity mice are approximately 10 times more active than the low activity mice. The hyperactive lines of mice (H1,H2) exhibit a dose dependent decrease in open-field activity following methamphetamine treatment, the control mice exhibit an increase in open-field activity and the low activity mice show no change in activity following methamphetamine treatment. These mice may serve as an appropriate animal model for the evaluation of locomotor activity as well as a model for the hyperactivity syndrome seen in childhood. Motor activity levels will be evaluated in the mice from 12 through 50 days of age. The effects of stimulant drugs on locomotor activity in the three lines of mice will be made at 12, 20 and 50 days of age. Shuttle box escape-avoidance behavior will be evaluated in the mice at 26 and 50 days of age and the effects of stimulant drugs on this behavior determined. The drugs that will be evaluated are; methamphetamine, d-amphetamine, l-amphetamine, and methylphenidate. The circadian rhythm of locomotor activity will be determined in adult mice over a 48 hour period. The effects of methamphetamine on this circadian rhythm will be examined. Catecholamine function in the brains of the three lines of mice will be evaluated and related to locomotor activity differences between the mice. The biochemical parameters that will be evaluated include tyrosine hydroxylase, catecholamine levels, catecholamine turnover, and uptake and release of catecholamines. The effects of four diet treatments, high sucrose, intermediate sucrose, no-sucrose and food dye administration, will be evaluated for their effects on the locomotor activity of the mice and on catecholamine function in the brains of the three lines of mice. Sucrose diets will be administered between 22 and 50 days of age, and the food dye mixture will be administered between days 5 and 50 days of age. The mice will be fed either a high sucrose (65%) diet, an intermediate sucrose diet (20%), a no-sucrose diet or a mixture of food dyes (3 mg/kg/day). We hope to provide more complete information on the relationship between locomotor activity, catecholamine function in the central nervous system, and dietary sugar and food dye ingestion.
| Masserano, J M; Barta, L (1989) Effects of dopaminergic and GABAergic antagonists on methamphetamine-induced locomotor activity in mice selectively bred for their differences in locomotor activity. Proc West Pharmacol Soc 32:195-9 |
