Serotonergic modulation of carbachol-induced rhythmic activity in hippocampal slices.
Fast rhythmic activity in a frequency range between 20 and 40 Hz occurs in vitro in hippocampal area CA3 after activation of muscarinic receptors. Here we show that carbachol-induced rhythmic activity is modulated by serotonin (5-HT). Spectral analysis reveals that 5-HT (0.3-30 microM) decreases power, but not frequency, of rhythmic activity in a concentration-dependent and reversible manner. The 5-HT(1A) agonists 8-OH-DPAT and buspirone mimic the effect of 5-HT, whereas the selective 5-HT(1A) receptor antagonist WAY-100635 (1 microM) significantly prevents the effect of 5-HT. In contrast to the effect of 5-HT(1A) agonists, the 5-HT(2) agonist DOI increases spectral power and prevents the reduction of spectral power by 5-HT. Application of WAY-100635 alone has no effect on rhythmic activity. Likewise, the 5-HT(2) antagonist ritanserin (10 microM) does not affect rhythmic activity, or its reduction by 5-HT. Finally, the 5-HT re-uptake inhibitor fluoxetine significantly decreases rhythmic activity in the presence of a low concentration of 5-HT, suggesting that 5-HT released from terminals in the slice likely reduces rhythmic activity. These results strongly implicate 5-HT(1A) and 5-HT(2) receptors in the modulation of spectral power of carbachol-induced rhythmic activity and that 5-HT(1A) receptors are responsible for the prevailing effect of 5-HT.
Krause
Michael
M
Tensor Biosciences, Irvine, CA 92612, USA. mkrause@cns.bcm.tmc.edu
Jia
Yousheng
Y
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D002217:Carbachol