The direct D2 dopamine receptor agonist RU 24926, administered subcutaneously to mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic effect, assessed as the jump latency from a hot plate (55 degrees C). The analgesic effect induced by 0.25 mg/kg RU 24926 was dose dependently antagonized by the preferential D2 dopamine receptor antagonist haloperidol (ID50 = 15.1 +/- 3.3 micrograms/kg sc) as well as by the opioid receptor antagonist naloxone (ID50 = 0.59 +/- 0.17 mg/kg sc). The reversion of RU 24926-induced analgesia by naloxone was not accompanied by a reversion of hypothermia. Semi-chronic administration of RU 24926 (2.5 mg/kg, sc, 3 times a day for 3 days) completely desensitized to the analgesic effect induced by a 0.25 mg/kg test dose of RU 24926 and partially reduced the analgesic effect of low doses of morphine (0.5, 1, 1.5 mg/kg). Conversely, semi-chronic administration of morphine (32 mg/kg sc, twice daily for 4 days) completely desensitized the analgesic effect induced by a 2 mg/kg test dose of morphine and partially reduced the analgesic effect of RU 24926 (0.25, 0.5 and 1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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