Dramatic limbic and cortical effects mediated by high affinity PCP receptors.

Using Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique, the psychotomimetic drug, phencyclidine (PCP, "angel dust") dramatically increased metabolism in diencephalic and telencephalic brain regions known to be rich in high affinity PCP receptors. These effects were greatest in the limbic circuit described in 1937 by the neurologist James Papez (mammillary bodies, anterior thalamus, cingulate gyrus, entorhinal cortex, hippocampus, fornix) and the terminal zones of dopaminergic projections. Caudal to the prefrontal cortex, the cerebral cortex developed an anterior-posterior metabolic gradient somewhat similar to that reported in schizophrenia. Brainstem areas were generally unaffected. These data 1) provide functional data to support Papez' assertion that his central limbic circuit may be important in emotional expression, 2) reaffirm the potential importance of dopaminergic function in psychotic-like behaviors, 3) provide an animal model for schizophrenia, and 4) establish that PCP uses high affinity PCP receptor binding sites to express its psychobiological effects.