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Decrease in rat striatal dopamine synthesis and metabolism in vivo by metabolically stable adenosine receptor

S Myers, T A Pugsley

|June 4, 1986

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Stable adenosine analogs, R-N-(1-methyl-2-phenylethyl)adenosine (R-PIA) and 5'-deoxy-5'- (ethylamino)-5'-oxoadenosine (NECA), reduce dopamine synthesis and release in rat striata. This effect is mediated via adenosine receptors.

Area of Science:

Neuroscience
Pharmacology

Background:

Dopamine (DA) synthesis and release are critical for motor control.
Adenosine analogs are known to modulate neurotransmitter systems.

Purpose of the Study:

To investigate the effects of stable adenosine analogs on dopamine synthesis and release in vivo.
To determine the role of adenosine receptors in mediating these effects.

Main Methods:

Administration of adenosine analogs (R-PIA, NECA, CHA) and an adenosine receptor antagonist (8-cyclopentyltheophylline) to rats.
Measurement of striatal dihydroxyphenylalanine (DOPA) and 3-methoxytyramine (3-MT) levels.
Analysis of dopamine synthesis and release rates.

Main Results:

R-PIA and NECA dose-dependently decreased striatal DOPA accumulation and 3-MT levels, indicating reduced DA synthesis and release.

Related Experiment Videos

N-Cyclohexyladenosine (CHA) decreased 3-MT levels, suggesting an effect on DA release.

The S-isomer of PIA had no significant effect.

8-Cyclopentyltheophylline antagonized the effects of R-PIA, confirming adenosine receptor mediation.

Conclusions:

Stable adenosine analogs R-PIA and NECA decrease in vivo dopamine synthesis and release from rat striatal nerve terminals.
These effects are mediated through adenosine receptors.
Adenosine analogs represent a potential therapeutic target for conditions involving dopamine dysregulation.