Effects of DA D1 and D2 antagonists on the sensitisation to the motor effects of morphine in mice

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Acute morphine administration produces hyperactivity in mice and repeated treatment induces an enhancement of this effect. In this experiment, we study the sensitisation to the hyperactivity induced by intermittent morphine administration (40 mg/kg) and the effects of dopamine (DA) antagonists on this phenomenon. Animals received three injections, separated by 48 h, and after each injection, their activity was registered between 30 and 60 min. In Experiment 1, animals were divided into two groups, which received saline and morphine (S–S–M) or only morphine (M–M–M). In Experiment 2, animals were divided into 12 groups. Half, which was designed to study the effects of DA antagonists on the acquisition of morphine sensitisation, received morphine plus 0.125, 0.25, or 0.5 mg/kg SCH 23390 or raclopride in the two first administrations and only morphine in the third (M+SCH–M+SCH–M; M+R–M+R–M). The other groups, designed to study the effects of DA antagonists on the expression of morphine sensitisation, received morphine in the two first administrations and morphine plus DA antagonists in the last injection (M–M–M+SCH; M–M–M+R). Intermittent morphine administration produces greater hyperactivity than acute morphine. DA D1 antagonists reduce acquisition and block expression of sensitisation, while DA D2 antagonists only affect expression with the intermediate and high dose. These results support the implication of DA in the behavioural sensitisation of morphine in mice.