Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, an

Seeman P, Guan HC, Hirbec H.
Synapse. 2009 Aug;63(8):698-704.

Although it is commonly stated that phencyclidine is an antagonist at
ionotropic glutamate receptors, there has been little measure of its potency on other
receptors in brain tissue. Although we previously reported that phencyclidine stimulated
cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine
did not stimulate D2 receptors in homogenates of rat brain striatum. This study,
therefore, examined whether phencyclidine and other hallucinogens and psychostimulants
could stimulate the incorporation of [35S]GTP-g-S into D2 receptors in homogenates
of rat brain striatum, using the same conditions as previously used to study the
cloned D2 receptors. Using 10 lM dopamine to define 100% stimulation, phencyclidine
elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration
of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM
for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120
nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM
for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand
[3H]domperidone. The incorporation was inhibited by the presence of 200 lM guanylylimidodiphosphate
and also by D2 blockade, using 10 lM S-sulpiride, but not by D1
blockade with 10 lM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited
the stimulation by phencyclidine, which may explain negative results by others. It is
concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate
dopamine D2 receptors at concentrations related to their behavioral actions.