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Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake
Published on: September 21, 2017
Neuroleptics and dopamine transporters
1Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada. readert@ere.umontreal.ca
Neurochemical Research
|March 3, 1998
Summary
Neuroleptic drugs like haloperidol and clozapine alter dopamine D1 and D2 receptors but not dopamine transporters in rat brains. This suggests dopamine receptors, not transporters, are the primary targets for these medications.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Neuroleptic medications are crucial for treating psychosis.
- Their precise molecular targets, particularly dopamine receptors and transporters, remain an area of active research.
- Understanding these interactions is key to developing more effective treatments.
Purpose of the Study:
- To investigate the impact of chronic haloperidol and clozapine treatment on dopamine transporters and dopamine receptors in the rat forebrain.
- To determine if changes in dopamine receptor density correlate with dopamine transporter levels.
- To elucidate the primary targets of neuroleptic drugs.
Main Methods:
- Adult rats were administered haloperidol, clozapine, or saline for 21 days.
- Dopamine D1 receptors were labeled and quantified using [3H]SCH23390.
- Dopamine D2 receptors were assessed using [3H]raclopride.
- Dopamine transporter densities were measured with [125I]RTI-121.
Main Results:
- Clozapine increased dopamine D1 receptors in specific brain regions (nucleus accumbens, neostriatum, substantia nigra).
- Both haloperidol and clozapine increased dopamine D2 receptors in various neostriatal areas, with haloperidol showing broader effects.
- Dopamine transporter densities remained unchanged following both neuroleptic treatments.
Conclusions:
- Dopamine transporters are resistant to chronic haloperidol and clozapine treatment.
- These findings suggest dopamine transporters are unlikely to be the primary targets of these neuroleptic drugs.
- Dopamine receptor up-regulation can occur independently of dopamine transporter levels, indicating distinct regulatory mechanisms.
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