PCP‐induced alterations in cerebral glucose utilization in rat brain: Blockade by metaphit, a PCP‐receptor‐acylating agent

Abstract

The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [14C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

Effects of Sustained Phencyclidine Exposure on Sensorimotor Gating of Startle in Rats

“…In rats, acute administration of PCP produces changes in behavior (Mansbach and Geyer, 1989), neurochemistry (Snell et al 1988), and brain metabolism (Tamminga et al 1987;Weissman et al 1989;Ellison and Keys 1996) that have been used to model pathological processes associated with schizophrenia. Long-standing changes in behavioral and brain measures also result from sustained PCP exposure in rats.…”

Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists

“…For example, several studies suggest that cortical glucose metabolism is increased regionally in animals administered NMDA antagonists (Clow et al 1991;Kurumaji and McCulloch 1990;Nehls et al 1988;Tamminga et al 1987). Similarly, ketamine increases frontal cortex cerebral blood flow and glucose metabolism in healthy human subjects (Breier et al 1997) and schizophrenic patients (Lahti et al 1995a).…”

Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers

“…NMDA receptors are located throughout the mammalian brain, with highest densities in the cerebral cortex, limbic system, and striatum (13). Autoradiographic studies of PCP and ketamine administration in rodents demonstrate activation in limbic and some cortical regions (14)(15)(16)(17). Low doses tend to focally activate the neocortex and limbic structures, while higher doses cause more homogeneous activation throughout these areas.…”

“…Low doses tend to focally activate the neocortex and limbic structures, while higher doses cause more homogeneous activation throughout these areas. Deactivation in somatosensory and auditory systems has been reported (14)(15)(16)(17), and in the case of PCP there is some evidence that acute activation predominates, with deactivation occurring 24 hours later (18). In a [ 15 O]H 2 O positron emission tomography (PET) study of five patients with schizophrenia (19), ketamine caused an increase in blood flow in the anterior cingulate and a decrease in blood flow in the hippocampus and primary visual cortex.…”