Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat

Synapse. 2004 Sep 15;53(4):202-7. doi: 10.1002/syn.20054.

Abstract

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Microdialysis
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Serotonin, 5-HT2 / drug effects
  • Receptors, Serotonin, 5-HT2 / metabolism*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Receptors, Serotonin, 5-HT2
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Acetylcholine