Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex

Br J Pharmacol. 2000 Mar;129(5):1028-34. doi: 10.1038/sj.bjp.0703139.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Biogenic Amines / metabolism
  • Brain Chemistry / drug effects
  • Dioxanes / administration & dosage
  • Dioxanes / pharmacology
  • Dioxoles / administration & dosage
  • Dioxoles / pharmacology
  • Dopamine / metabolism*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Injections, Subcutaneous
  • Male
  • Microdialysis
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin / metabolism
  • Serotonin Agents / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Serotonin Uptake Inhibitors / pharmacology
  • Synapses / drug effects*

Substances

  • Biogenic Amines
  • Dioxanes
  • Dioxoles
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Agents
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • osemozotan
  • Dopamine