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Cyclo (His-Pro), d-amphetamine and striatal dopamine: a microdialysis study
A Levy1, M J Stillman, T M Rauch
1U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760.
Brain Research Bulletin
|July 1, 1991
Summary
Cyclo(His-Pro) (CHP) reduces dopamine levels in rat striatum after amphetamine administration, suggesting a depletion mechanism rather than reuptake interference. This indicates potential involvement of other neurotransmitters in CHP
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Cyclo(His-Pro) (CHP) is a cyclic dipeptide with potential neuromodulatory effects.
- Dopamine (DA) neurotransmission in the striatum is crucial for motor control and reward.
- Amphetamine is a psychostimulant that affects dopaminergic pathways.
Purpose of the Study:
- To investigate the mechanism by which CHP influences dopaminergic activity in the rat striatum.
- To determine if CHP affects dopamine release, reuptake, or metabolism.
- To explore the interaction between CHP and d-amphetamine in vivo.
Main Methods:
- In vivo microdialysis was used to monitor extracellular dopamine (DA) and its metabolites (DOPAC, HVA) in the rat striatum.
- Rats were pretreated with CHP or saline, followed by d-amphetamine administration.
- Dialysate samples were analyzed using high-performance liquid chromatography with electrochemical detection (HPLC-EC).
Main Results:
- CHP pretreatment significantly attenuated the d-amphetamine-induced increase in extracellular DA levels in the striatum (p < 0.05).
- No significant differences in DOPAC or HVA levels were observed between CHP-treated and saline-treated rats.
- The findings suggest CHP does not interfere with d-amphetamine-induced DA reuptake inhibition.
Conclusions:
- CHP likely attenuates the dopaminergic response to d-amphetamine through striatal DA depletion, potentially via tyrosine hydroxylase (TH) inhibition.
- A dissociation may exist between the behavioral effects of amphetamine and its direct impact on striatal DA levels.
- Intracellular DA in the striatum may exist in excess relative to extracellular DA, supporting a model where amphetamine releases newly synthesized, extravesicular DA.