Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex.
5-Hydroxytryptamine (5-HT) plays a role in the regulation of 3, 4-dihydroxyphenylethylamine (dopamine) neurons in the brain, but the precise mechanism of regulation by 5-HT(1A) receptors of dopamine release has not been defined. The present study describes the effect of 5-¿3-[[(2S)-1,4-benzodioxan-2ylmethyl]amino]propoxy¿-1, 3-benzodioxole HCl (MKC-242), a highly potent and selective 5-HT(1A) receptor agonist, on dopamine release in the prefrontal cortex using microdialysis in the freely moving rat. Subcutaneous injection of MKC-242 (0.3 - 1.0 mg kg(-1)) increased extracellular levels of dopamine in the prefrontal cortex. The effect of MKC-242 in the prefrontal cortex was antagonized by pretreatment with the selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY100635; 1 mg kg(-1), i.p.). Local application of WAY100635 (10 microM) via a microdialysis probe antagonized the effect of systemic MKC-242 in an increasing dopamine release, and locally infused 8-hydroxy-2-(di-n-propylamino)tetralin (10 microM) increased dopamine release in the prefrontal cortex. MKC-242 increased cortical dopamine release in the rats pretreated with 5, 7-dihydroxytryptamine (150 microgram, i.c.v.) that caused an almost complete reduction in cortical 5-HT content. The effect of MKC-242 to increase dopamine release was also observed in the hippocampus, but not in the striatum or nucleus accumbens. Fluoxetine, a selective serotonin reuptake inhibitor, increased dopamine release in the prefrontal cortex, but not in the nucleus accumbens, while buspirone, a 5-HT(1A) receptor agonist, increased dopamine release in both brain regions. The present results indicate that activation of postsynaptic 5-HT(1A) receptors increases dopamine release in a brain region-specific manner.
Sakaue
M
M
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamado-oka, Suita, Osaka 565-0871 Japan.
Somboonthum
P
P
Nishihara
B
B
Koyama
Y
Y
Hashimoto
H
H
Baba
A
A
Matsuda
T
T
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*
D015116:5,7-Dihydroxytryptamine; D001679:Biogenic Amines; D004146:Dioxanes; D004149:Dioxoles; D004298:Dopamine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C096294:osemozotan