- To determine locomotion following acute amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) administration.
- To determine locomotor sensitization following repeated amphetamine or MDMA exposure.
- To identify neurochemical and molecular targets underlying drug sensitivity.
Approach and Progress
The plan is to further characterize test class animals already identified in primary screens to exhibit vulnerability to addiction.
Mice identified as outliers by both pharmacological and non-pharmacological screens will be tested. This will allow us to determine whether mice exhibiting vulnerability to addiction by means other than cocaine will respond to amphetamine or MDMA. We will also determine whether response to cocaine can be generalized to other psychoactive drugs. Amphetamine and MDMA were chosen because they elicit behavioral effects through different mechanisms. Amphetamine acts by increasing the release of dopamine from presynaptic nerve terminals and inhibiting the reuptake of dopamine from the synapse. MDMA on the other hand, evokes hyperactivity by increasing the release of dopamine and serotonin. Furthermore, the pattern of behavior evoked by MDMA is different from that of amphetamine.
All testing will be conducted in activity chambers (Med Associates). Initially, dose-response profiles will be determined. Doses will range from 1 to 10 mg/kg for each drug. From the dose-response profiles appropriate doses will be selected for locomotor sensitization.