title: First and second generation antipsychotics influence hippocampal gamma oscillations by interactions with 5-HT3 and D3 receptors.
abstract: OBJECTIVE
  Disturbed cortical gamma band oscillations (30-80 Hz) have been observed in schizophrenia: positive symptoms of the disease correlate with an increase in gamma oscillation power, whereas negative symptoms are associated with a decrease.
  
  
  METHODS
  Here we investigated the effects of first and second generation antipsychotics (FGAs and SGAs, respectively) on gamma oscillations. The FGAs haloperidol, flupenthixol, chlorpromazine, chlorprothixene and the SGAs clozapine, risperidone, ziprasidone, amisulpride were applied on gamma oscillations induced by acetylcholine and physostigmine in the CA3 region of rat hippocampal slices.
  
  
  RESULTS
  Antipsychotics inhibited the power of gamma oscillations and increased the bandwidth of the gamma band. Haloperidol and clozapine had the highest inhibitory effects. To determine which receptor is responsible for the alterations in gamma oscillations, the effects of the antipsychotics were plotted against their pK(i) values for 19 receptors and analysed for correlation. Our results indicated that 5-HT(3) receptors have an enhancing effect on gamma oscillations whereas dopamine D(3) receptors inhibit them. To test this prediction, m-chlorophenylbiguanide, PD 128907 and CP 809101, selective agonists at 5-HT(3) , D(3) and 5-HT(2C) receptors were applied and revealed that 5-HT(3) receptors indeed enhanced the gamma power whereas D(3) receptors reduced it. As predicted, 5-HT(2C) receptors had no effects on gamma oscillations.
  
  
  CONCLUSIONS
  Our data suggest that antipsychotics alter hippocampal gamma oscillations by interacting with 5-HT(3) and dopamine D(3) receptors. Moreover, a correlation of receptor affinities with the biological effects can be used to predict targets for the pharmacological effects of multi-target drugs.
authors: Institute of Neurophysiology, Charité Universitätsmedizin Berlin, Berlin, Germany NeuroCure Research Centre, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Steffen B
authors: SB
authors: Schulz
authors: Karin E
authors: KE
authors: Heidmann
authors: Arpad
authors: A
authors: Mike
authors: Zin-Juan
authors: ZJ
authors: Klaft
authors: Uwe
authors: U
authors: Heinemann
authors: Zoltan
authors: Z
authors: Gerevich
mesh_terms: D000109:Acetylcholine; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D010830:Physostigmine; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D050637:Receptors, Dopamine D3; D044406:Receptors, Serotonin, 5-HT3; D010830:Physostigmine; D000109:Acetylcholine