Related Experiment Videos
Drug dependence, synaptic plasticity, and tissue plasminogen activator
Kiyofumi Yamada1, Taku Nagai, Toshitaka Nabeshima
1Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Japan. kyamada@p.kanazawa-u.ac.jp
Journal of Pharmacological Sciences
|February 3, 2005
Summary
Tissue plasminogen activator (tPA) is crucial for drug dependence. Reduced tPA in mice impaired responses to morphine and methamphetamine, indicating tPA
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The mesocorticolimbic dopaminergic system is vital for drug reinforcement.
- Synaptic plasticity in this system contributes to drug dependence.
Purpose of the Study:
- To investigate the role of tissue plasminogen activator (tPA) in the development of drug dependence.
- To explore tPA's contribution to the neurobiological changes underlying addiction.
Main Methods:
- Utilized DNA microarray screening to assess tPA mRNA expression in drug-dependent rat models.
- Employed gene deletion (tPA-/- mice) and pharmacological interventions to evaluate tPA's function.
- Measured conditioned place preference, dopamine release, and locomotor activity.
Main Results:
- Drug dependence (morphine, methamphetamine) significantly increased tPA mRNA expression and enzyme activity in the nucleus accumbens.
- tPA-/- mice exhibited reduced morphine- and methamphetamine-induced conditioned place preference and behavioral responses.
- Restoring tPA or plasmin levels in the nucleus accumbens reversed these deficits.
Conclusions:
- Tissue plasminogen activator (tPA) plays a significant role in the neuroadaptations associated with drug dependence.
- tPA contributes to the development and maintenance of addiction-related behaviors.
- Targeting tPA may offer a novel therapeutic strategy for substance use disorders.