The 5-HT1A receptor antagonist (S)-UH-301 decreases dopamine release in the rat nucleus accumbens and striatum.
In this study we employed in vivo microdialysis to examine the effects of the selective 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-UH-301] on extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens (NAC) and dorsal striatum of awake freely moving rats. Systemic administration of (S)-UH-301 (1.25, 2.5, 5.0 mg/kg s.c.) dose-dependently decreased extracellular concentrations of DA, DOPAC and HVA in the NAC. (S)-UH-301 (2.5 mg/kg s.c.) also decreased DA, but not DOPAC and HVA, concentrations in the striatum. Infusion of low concentrations (1, 10 microM) of (S)-UH-301 into either the NAC or the striatum did not affect DA levels, while only the highest concentration (1,000 microM) significantly decreased DA levels in both areas. Similarly, infusion of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-8-OH-DPAT] only in high concentrations (100, 1,000 microM) decreased DA levels in both regions. These data suggest that (S)-UH-301 decreases DA release both in the NAC and the striatum probably indirectly via its purported DA-D2/D3 receptor agonistic properties. However, the observed inhibitory effect of (S)-UH-301 on DA release in the studied brain regions may also be explained, at least partly, by a serotonergic influence on the DA systems, acting at 5-HT1A receptor sites located elsewhere in the brain.
Nomikos
G G
GG
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Arborelius
L
L
Höök
B B
BB
Hacksell
U
U
Svensson
T H
TH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; C064282:UH 301; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004298:Dopamine; D006719:Homovanillic Acid