Clozapine, glycine and NMDA all reduce the frequency of high frequency oscillations in the nucleus accumbens of freely moving mice

• Autorzy: Olszewski M. , Piasecka J. , Whittington M.A. , Kasicki S. , Hunt M.J.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: To examine the effect of NMDA receptor antagonists and antipsychotics on high frequency oscillations (HFO, 130–180 Hz) recorded in local field potentials from the nucleus accumbens (NAc) of freely moving mice. To identify the receptors that may underlie clozapine-induced reductions in HFO frequency. METHODS: Freely moving mice, with electrodes implanted in the NAc, received systemic injection of NMDAR antagonists (ketamine and MK801); antipsychotic compounds (clozapine and haloperidol) were administered to MK801-pretreated mice. We attempted to identify the receptors mediating clozapine-induced reductions in HFO frequency using a pharmacological agents targeting 5HT1A, 5HT2A, histamine H3 and NMDA receptors. RESULTS: Ketamine and MK801 dose dependently increased the power of HFO and produced small increases in their frequency. Clozapine, dose dependently reduced the frequency of HFO whereas haloperidol had little effect on HFO. Systemic injection of glycine, which has antipsychotic properties, and allosterically modulates NMDAR, reduced the frequency of HFO to values comparable after injection of clozapine. Systemic administration of NMDA produced a short-lasting reduction in MK801-enhanced HFO frequency. Other receptors known to be targets for clozapine, namely 5-HT2A, 5-HT7 and histamine H3 receptors had no effect on MK801-enhanced HFO, although we did find a reduction in HFO frequency after injection of 5HT1A agonist. CONCLUSIONS: These results show that NMDAR antagonists and antipsychotics produce broadly similar fundamental effects on HFO in mice and rats. Stimulation of NMDAR (directly, or through the glycine site) as well as activation of 5HT1A receptors, reduces the frequency of MK801-enhanced HFO suggesting that atypical antipsychotic drugs may alter HFO by interacting with NMDA and 5HT1A receptors. Project funded by the National Center of Science DEC-2011/03/B/ NZ4/03053.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S106

Twórcy

autor

Olszewski M.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Piasecka J.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Whittington M.A.

• Hull York Medical School, University of York, York, U.K.

autor

Kasicki S.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Hunt M.J.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland