Different receptor subtypes are involved in the serotonin-induced modulation of epileptiform activity in rat frontal cortex in vitro.
The frontal cortex is innervated by serotonergic terminals from the raphe nuclei and it expresses diverse 5-HT receptor subtypes. We investigated the effects of 5-HT and different 5-HT receptor subtype-selective agonists on spontaneous discharges which had developed in rat cortical slices perfused with a Mg2+-free medium and the GABA(A) receptor antagonist picrotoxin. The frequency of synchronous discharges, recorded extracellularly in superficial layers (II/III) of the frontal cortex, was dose-dependently enhanced by 5-HT (2.5-40 microM). That excitatory effect was blocked by the 5-HT2 receptor selective antagonist ketanserin. The 5-HT2A/2C receptor-selective agonist DOI and the 5-HT4 receptor agonist zacopride also increased the frequency of spontaneous discharges. In the presence of ketanserin, 5-HT decreased the discharge rate; a similar effect was observed when the 5-HT1A receptor agonist 8-OH-DPAT or the 5-HT1B receptor agonist CGS-12066B was applied. The 5-HT3 receptor agonist m-CPBG was ineffective. In conclusion, 5-HT produces multiple effects on epileptiform activity in the frontal cortex via activation of various 5-HT receptor subtypes. The excitatory action of 5-HT, which predominates, is mediated mainly by 5-HT2 receptors. The inhibitory effects can be attributed to activation of 5-HT1A and 5-HT1B receptors.
Bobula
B
B
Department of Physiology, Polish Academy of Sciences, Kraków.
Zahorodna
A
A
Bijak
M
M
D000818:Animals; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D016166:Free Radical Scavengers; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin