The effect of MK-801 and SCH23390 on the expression and sensitization of morphine-induced oral stereotypy.

Repeated high doses of morphine sulfate, administered in a 24-36 h period, stimulates the expression of oral stereotypy in rats. Sensitization to this effect of morphine is demonstrated by the reexpression of the stereotypy by the administration of 4.0 mg/kg of morphine one week following the original exposure. To investigate the role of N-methyl-D-aspartic acid (NMDA) and D1 dopamine (DA) receptors in the acute expression and sensitization of morphine-induced oral stereotypy, rats were administered four injections of morphine (10.0 mg/kg) one injection every 12 h and observed for the expression of stereotypic behaviors following pretreatment with selective antagonists. Pretreatment with the NMDA antagonist, MK-801 (0.7 mg/kg), before each of the four morphine injections antagonized both the initial expression of oral stereotypy and the development of sensitization. In contrast, the DA D1 receptor antagonist SCH23390 (40.0 micrograms/kg) administered during the four high-dose treatments with morphine antagonized the initial expression of oral stereotypy and not the development of sensitization. These findings implicate glutamate's action at the NMDA receptor in both the acute expression of morphine-induced oral stereotypy, and the development of sensitization of this morphine effect, whereas DA D1 receptors may only be involved in the acute expression of the stereotypy.