Authors: Gary Gilmour Elsa Y Pioli Sophie L Dix Janice W Smith Michael W Conway Wendy T Jones Sally Loomis Rebecca Mason Shahram Shahabi Mark D Tricklebank
Publish Date: 2009/05/07
Volume: 205, Issue: 2, Pages: 203-216
Abstract
To further resolve such conjecture the present study systematically compared eight different NMDA receptor antagonists MK801 PCP ketamine memantine SDZ 220581 Ro 256981 CP 101606 and NVPAAM077 in a series of variable interval VI schedules of reinforcement Aspects of motivation as indexed in these tasks may well be impaired in schizophrenia and undoubtedly impact on the capacity to perform more complex explicit tasks of cognitionAn initial locomotor activity assessment demonstrated that all antagonists tested except the NR2Asubunit preferring antagonist NVPAAM077 induced hyperactivity albeit of greatly differing magnitudes qualities and temporal profiles Three distinct patterns of antagonist effect were evident from the VI assays used a uniform decrease in responding produced by S+ketamine memantine and NVPAAM077 a uniform increase in responding caused by the NR2Bsubunit preferring antagonists Ro 256981 and CP 101606 and variable bidirectional effects of PCP SDZ 220581 and MK801Despite nominally common mechanisms of action and often presumed biological equivalence the NMDA antagonists tested produced very diverse effects on the expression of instrumental action Other aspects of responding were left intact including switching and matching behaviours and the ability to respond to conditional stimuli The implications of such findings with regard to animal modelling of schizophrenic psychotic symptoms are manifold
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