Lack of specific effects of selective D(1) and D(2) dopamine antagonists vs. risperidone on morphine-induced hyperactivity

Pharmacol Biochem Behav. 2000 May;66(1):189-97. doi: 10.1016/s0091-3057(00)00207-0.

Abstract

In the present study, three different dopamine antagonists were challenged in order to counteract hyperactivity induced by 50 mg/kg of morphine. A wide range of doses of morphine (50, 25, 12.5, 6.25, or 3.12 mg/kg) were evaluated on spontaneous locomotor activity. A significant increase was observed only with the two higher doses tested (25 and 50 mg/kg). No decrease was found with any of the doses used at any period of time. After analyzing doses of SCH 23390 (0.5, 0.1, and 0.05 mg/kg), raclopride (0.5, 0.25, and 0.125 mg/kg) and risperidone (0.1, 0.05, and 0.025 mg/kg) administered alone, only the 0.5 mg/kg dose of SCH 23390 decreased locomotor activity. The three compounds counteracted morphine-induced hyperactivity, but with SCH 23390 it was only achieved with the dose of 0.5 mg/kg, which also decreased spontaneous locomotor activity and induced catalepsy. On the other hand, raclopride and risperidone neutralized morphine-induced hyperactivity at doses that did not affect locomotor activity, although the former induced catalepsy when administered with morphine. It is concluded that although the blockade of D(1) and D(2) DA receptors decreases morphine-induced hyperactivity, this action is not specific, contrary to the action of risperidone, which counteracts this hyperactivity without any other motor effects.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Catalepsy / chemically induced
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Male
  • Mice
  • Morphine / pharmacology*
  • Motor Activity / drug effects*
  • Narcotics / pharmacology*
  • Raclopride / pharmacology
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Risperidone / pharmacology*

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Narcotics
  • Receptors, Dopamine D1
  • Raclopride
  • Morphine
  • Risperidone