Phencyclidine and other hallucinogens and psychostimulants can activate dopamine D2 receptors in rat brain tissue, contrary to some earlier reports. Using rat striatum homogenates, phencyclidine achieved 46% of the maximum stimulation produced by dopamine, with a half-maximum concentration of 70 nM. Other compounds, including LSD, salvinorin A, R-modafinil, ketamine, and dizocilpine, also stimulated D2 receptors at concentrations related to their behavioral effects. The stimulation was blocked by a D2 antagonist and by hypertonic buffer containing sodium chloride, which may explain why previous studies failed to observe this effect.
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.