Levels of Ionotropic Glutamate and Muscarinic Receptors in Three Animal Models of Schizophrenia

Abstract

There are well validated rodent paradigms of schizophrenia which are based on environmental manipulation (e.g. altered rearing conditions) or drug challenges. These manipulations induce behavioural changes in rodents that are thought to involve neuronal circuitry similar to the ones that are affected by the pathophysiology of the disorder. This study has investigated whether three such rodent paradigms (isolation rearing, neonatal PCP treatment or sub-chronic PCP treatment) are associated with changes in muscarinic receptors (CHRMs) or ionotropic glutamate receptors, some of which have been reported to be altered in the CNS of subjects with schizophrenia. ( 3 H)pirenzepine (CHRM1), ( 3 H)4DAMP (CHRM1/CHRM3), ( 3 H)MK801 (NMDA receptors) and ( 3 H)kainate (kainate receptors; KAR) binding were measured using in situ radioligand binding and autoradiography. Isolation rearing caused widespread decreases in ( 3 H)4DAMP (p = 0.01) and ( 3 H)kainate binding (p = 0.03). Neonatal PCP caused widespread increases in ( 3 H)4DAMP binding (p <0.0001), whereas sub-chronic PCP treatment caused widespread decreases in the binding of that radioligand (p < 0.002) and widespread increases in (3H)MK801 binding (p < 0.0001). There were no changes in ( 3 H)pirenzepine binding to CHRM1 receptors in any paradigm or no significant within region changes in the binding of any radioligand. In conclusion, in the absence of any changes in CHRM1 receptors, our ( 3 H)4DAMP and the binding of (3H)MK801 data would suggest that different rodent paradigms cause variable changes in levels of CHRM3 and KAR in the rat CNS. Our data raises the possibility that such changes may, in part, modulate the behavioural differences that have been observed after isolation rearing, neonatal PCP treatment or sub-chronic PCP treatment.