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[Individual differences in the accelerating effect of methamphetamine, d-amphetamine and morphine on ambulatory
Abstract:
Several problems concerning the ambulatory activity were discussed from the viewpoint of drug assay using about 700 adult male mice of ddG strain. Each response pattern for 180 approximately 400 min obtained from the temporal changes of ambulatory activity after administration of methamphetamine (1 approximately 16 mg/kg s.c.), d-amphetamine (1.25 approximately 5 mg/kg s.c.) or morphine (5 approximately 20 mg/kg s.c.) was recorded and used for the data analysis. All the above mentioned drugs markedly accelerated the activity when the doses were optimal. However, the individual response to the drugs sometimes reached a 40- approximately 70-fold difference, even though both animal and measurement conditions were fixed as constant way as possible. The time when the experiments took place did not explain the individual differences, nor did the season or body weight of the animal. However, there was the possibility of colony differences. Animals with relatively high activity prior to drug administration tended to respond more forcibly after administration of the drugs. It was found from the statistical investigation that constant observation of over 1 hr using at least 15 animals was required in order to determine a standard effect of the drug. Furthermore, the accelerating effect of methamphetamine and d-amphetamine on the activity was observed to be dose-dependent when below 4 and 5 mg/kg was given, respectively. On the contrary, the effect decreased dose-dependently when higher doses were given as stereotyped behavior such as head-swaying, continuous sniffing and circular movements in opposition to the horizontal movements also developed dose-dependently. As the qualitatively different behavior could be simultaneously measured, the individual differences were more apparent.
Insights
Drug assays in mice reveal significant individual variability in ambulatory activity responses to methamphetamine, d-amphetamine, and morphine. Pre-existing activity levels and colony origin may influence outcomes, necessitating careful experimental design for reliable drug effect determination.
Area of Science:
- Pharmacology
- Neuroscience
- Animal Behavior
Context:
- Assessing drug effects on ambulatory activity in preclinical models is crucial for understanding behavioral pharmacology.
- Individual variability in animal responses poses challenges for standardizing drug assays.
- Previous studies often overlook the significant impact of individual differences on drug-induced behavioral changes.
Purpose:
- To investigate the sources of individual variability in ambulatory activity responses to psychostimulant drugs in mice.
- To determine optimal experimental parameters for reliable drug effect measurement in preclinical studies.
- To analyze dose-dependent effects and the emergence of stereotyped behaviors following drug administration.
Summary:
- Adult male ddG strain mice (N≈700) received methamphetamine, d-amphetamine, or morphine, with ambulatory activity monitored for 180-400 minutes.
- Significant individual differences (40-70 fold) in drug response were observed despite controlled conditions, with pre-existing activity and colony origin as potential factors.
- A minimum of 1 hour observation with at least 15 animals is recommended for establishing standard drug effects, with dose-dependent acceleration and subsequent stereotyped behaviors noted at higher doses.
Impact:
- Highlights the critical need for accounting for individual variability in animal models for accurate drug efficacy and safety assessments.
- Provides guidelines for experimental design, including sample size and observation duration, to improve the reliability of preclinical drug studies.
- Suggests that pre-drug activity levels and colony differences are key variables influencing drug response, informing future research directions.