The role of NMDA and AMPA/Kainate receptors in the consolidation of catalepsy sensitization

▶ Subchronic (daily) haloperidol administration leads to development of catalepsy sensitization. ▶ Co-treatment with the NMDA-antagonist MK-801 immediately after the cessation of the daily catalepsy tests attenuated the development of catalepsy sensitization. ▶ Co-treatment with the AMPA-antagonist GYKI 52466 immediately after the cessation of the daily catalepsy tests attenuated the development of catalepsy sensitization as well. ▶ In conclusion, the consolidation of haloperidol induced catalepsy sensitization is dependent on functional NMDA- and AMPA-receptors. Daily injection of the dopamine D2 receptor antagonist haloperidol is associated with the development of catalepsy sensitization in rats, which leads to a day to day increase of rigor and akinesia. The process of catalepsy sensitization incorporates different learning stages. Here we investigated the mechanisms underlying the consolidation of catalepsy sensitization. In particular, we asked whether NMDA- and non-NMDA (AMPA- and Kainate) receptors play a role in the consolidation of catalepsy sensitization. Accordingly, rats received post-training injections of the NMDA receptor antagonist MK-801 (single injection of either 0.1mg/kg or 0.25mg/kg; or a double injection of 0.1mg/kg immediately and 30min after test cessation) or of the AMPA/Kainate receptor antagonist GYKI 52466 (single injection of 5mg/kg). Our results showed that the consolidation of catalepsy sensitization was decelerated by both glutamatergic AMPA/Kainate- and NMDA-receptor antagonists. With the higher MK-801 dosage, the deceleration was stronger, suggesting a dose dependent mechanism. We hence affirmed a role for the ionotropic glutamate receptors in the consolidation process of catalepsy sensitization.