Dopamine agonist action of phencyclidine.

Phencyclidine, a psychotomimetic drug often used to model psychosis, directly activates dopamine D2 receptors, consistent with the dopamine hypothesis of psychosis. In rat cultured anterior pituitary cells, phencyclidine inhibited prolactin release by 50% at a concentration of 4 nM, indicating a potent dopamine-like agonist effect. This finding suggests that phencyclidine's psychotomimetic action may involve direct functional effects on dopamine receptors, rather than solely through glutamate pathways.

Study at a glance

Abstract

Although the psychotomimetic action of phencyclidine is often used to model a hypoglutamate theory of psychosis or schizophrenia, work also exists showing that phencyclidine has a significant affinity for the dopamine D2 receptor. The present study was done to determine whether phencyclidine has a direct functional dopamine-like action on cells. The effect of phencyclidine was tested on the release of prolactin from rat cultured anterior pituitary cells. It was found that the release of prolactin was 50% inhibited by 4 nM phencyclidine. This strong dopamine-like agonist action at the functional high-affinity state of the dopamine D2 receptor by the phencyclidine psychotomimetic is consistent with the dopamine hypothesis of psychosis.