Supersensitivity of striatal D2 dopamine receptors mediating inhibition of adenylate cyclase and stimulation of guanosine triphosphatase following chronic administration of haloperidol in mice

Adenylate cyclase and guanosine triphosphatase (GTPase) activities in response to dopamine (DA) were determined in membranes prepared from striata of mice treated with haloperidol for a period of 3 months. D1- and D2 receptor-mediated effects were investigated in the presence of 2 microM (-)-sulpiride and 0.1 microM SCH 23390, respectively. The drug treatment produced a 38% increase in the maximal inhibition of adenylate cyclase activity elicited by DA via D2 receptors. D1-mediated stimulation of adenylate cyclase was not affected. The enhanced D2 inhibition of adenylate cyclase was associated with a 45% increase in the stimulatory response of GTPase activity via D2 sites. These results indicate that D2 receptors linked to inhibition of adenylate cyclase and to stimulation of GTPase become supersensitive following in vivo chronic blockade of DA receptors.