SEROTONINERGIC MODULATION OF EXCITABILITY IN AREA CA1 OF THE IN-VITRORAT HIPPOCAMPUS

Intra- and extracellular recordings from the in vitro rat hippocampal slice preparation have been used to investigate the influence of serot oninergic, adrenergic and cholinergic receptor antagonists on the exci tability of CAI pyramidal neurones. The serotonin receptor antagonist 4-amino-N-(1-azabicyclo[2.2.2]oct-3 yl)-5-chloro-2-methoxybenzamide(E) -2-butenedioate (zacopride, 100 mu M) produced multiple population spi kes on the orthodromically evoked field potential, in contrast to the lack of effect of another serotonin antagonist 1 alpha H,3 alpha,5 alp ha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222, 30 mu M), as well as the cholinergic antagonists atropine (10 mu M) and hexamethonium (100 mu M) and the noradrenergic antagonist atenolol (10 mu M). Monosynapt ic inhibitory postsynaptic potentials (IPSPs) recorded in the presence of the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 mu M) and ketamine (50 mu M) were recorded from CAI pyramid al neurones. Zacopride (100 mu M) and MDL 72222 (30 mu M) both reduced the isolated IPSP to 54 +/- 9% (n = 8) and 78 +/- 4% (n = 3), respect ively. Neither of the cholinergic antagonists had any effect, while at enolol reduced the IPSP to 87 +/- 3% (n = 7) of the control IPSP. We p ropose that the difference in action of zacopride and MDL 72222 on the field potentials is due to zacopride activating postsynaptic 5HT(4) r eceptors on the pyramidal neurone, thereby reducing a Ca2+-activated K +-conductance. This, in combination with a 5HT(3) receptor-mediated re duction in gamma-aminobutyric acid (GABA)-ergic inhibition, leads to a n increase in pyramidal cell excitability evident as epileptic field p otentials.