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Updated: May 1, 2026
Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
The effect of early environmental manipulation on locomotor sensitivity and methamphetamine conditioned place
1Department of Psychology, University of Nevada Las Vegas, 4505 Maryland Parkway, Box 455030, Las Vegas, NV, USA.
Insights
Early life stress, like neonatal separation in rats, impacts adult behavior. Separated male rats showed increased activity with methamphetamine, but this stressor did not affect drug reward preference.
Area of Science:
- Neuroscience
- Behavioral Science
- Developmental Psychology
Background:
- Early life stress (ELS) negatively impacts neurological development and long-term health.
- Childhood abuse and neglect correlate with increased depression, risk-taking, and drug abuse.
- Neonatal separation in animal models serves as a crucial ELS paradigm.
Purpose of the Study:
- To investigate the long-term effects of ELS on drug-related behaviors.
- To examine sex-specific responses to methamphetamine following neonatal separation.
- To assess changes in neurotransmitter transporter gene expression after ELS.
Main Methods:
- Rat pups underwent daily 180-minute separation from postnatal days 2-8, or were handled as controls.
- Adult rats were tested for methamphetamine-induced conditioned place preference and locomotor activity.
- mRNA levels of norepinephrine and dopamine transporters were quantified in specific brain regions.
Main Results:
- Methamphetamine induced conditioned place preference similarly in all rats, irrespective of ELS or sex.
- Separated male rats exhibited heightened locomotor activity in response to methamphetamine compared to controls.
- Females were generally more active than males; ELS did not affect female locomotor activity or any mRNA levels.
Conclusions:
- Neonatal separation influences methamphetamine-induced locomotor activity in a sex-dependent manner.
- ELS, under these conditions, does not alter methamphetamine reward preference or transporter gene expression.
- These findings highlight the complex, sex-specific neurobiological consequences of early life stress.
Abstract:
Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 min per day during postnatal days 2-8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference.
