Effects of estrogen on acetylcholine release in frontal cortex of female rats: involvement of serotonergic neuronal systems

Brain Res. 2002 May 24;937(1-2):58-65. doi: 10.1016/s0006-8993(02)02465-4.


The effects of estrogen on cortically projecting cholinergic neurons were investigated using in vivo microdialysis to measure cortical basal acetylcholine (ACh) levels and serotonin (5-HT)-stimulated ACh release in frontal cortex of freely moving Wistar female rats. Bilateral ovariectomy (OVX) or sham operations were performed under anesthesia. Immediately after surgery, each OVX animal was subcutaneously implanted with pellet containing 0.1/0.5 mg of 17beta-estradiol (E(2)) or a vehicle. Nineteen days later, a transverse microdialysis probe was stereotaxically implanted in the frontal cortex (AP: +2.7 mm, DV: -2.5 mm relative to bregma). Two days later (21 days after beginning of estrogen treatment), in vivo microdialysis experimentation was conducted. Serum E(2) levels of animals with 0.1 and 0.5 mg-pellets were equivalent to those levels during diestrous and proestrous, respectively. Although the replacement of different amounts of E(2) produced significant changes in body weight, it failed to affect basal ACh levels in the frontal cortex. Systemically administered serotonin releasing agent, fenfluramine, significantly increased cortical ACh release in all animal groups. The fenfluramine's ability to increase ACh release was potentiated by E(2) replacement with a 0.5 mg-pellet. E(2)-induced enhancement was also observed when the selective 5-HT(1A) agonist, 8-hydroxy-2-(di-n-propylamino) tetralin, but not the 5-HT(2A/2C) agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, was administered. Therefore, the effect of estrogen on 5-HT-stimulated ACh release might be exerted partly via 5-HT(1A) receptors, and not via 5-HT(2) receptors. These results suggest that the positive effects of estrogen on cognitive functions might be mediated through the ACh-5-HT interactions.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Acetylcholine / metabolism*
  • Amphetamines / pharmacology
  • Animals
  • Cognition / drug effects
  • Cognition / physiology*
  • Diestrus
  • Drug Implants
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Estrogens / physiology*
  • Female
  • Fenfluramine / pharmacology
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Microdialysis
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology*
  • Ovariectomy
  • Proestrus
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Serotonin / physiology*
  • Serotonin Receptor Agonists / pharmacology


  • Amphetamines
  • Drug Implants
  • Estrogens
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Fenfluramine
  • Serotonin
  • Estradiol
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Acetylcholine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine