The effect of forced swim stress on morphine sensitization: Involvement of D1/D2-like dopamine receptors within the nucleus accumbens

Nucleus accumbens (NAc) plays an essential role in morphine sensitization and suppression of pain. Repeated exposure to stress and morphine increases dopamine release in the NAc and may lead to morphine sensitization. This study was carried out in order to investigate the effect of forced swim stress (FSS), as a predominantly physical stressor and morphine on the development of morphine sensitization; focusing on the function of D1/D2-like dopamine receptors in the NAc in morphine sensitization. Eighty-five adult male Wistar rats were bilaterally implanted with cannulae in the NAc and various doses of SCH-23390 (0.125, 0.25, 1 and 4 mu g/0.5 mu l/NAc) as a D1 receptor antagonist and sulpiride (0.25, 1 and 4 mu g/0.5 mu l/NAc) as a D2 receptor antagonist were microinjected into the NAc, during a sensitization period of 3 days, 5 min before the induction of FSS. After 10 min, animals received subcutaneous morphine injection (1 mg/kg). The procedure was followed by 5 days free of antagonist, morphine and stress; thereafter on the 9th day, the nociceptive response was evaluated by tail-flick test. The results revealed that the microinjection of sulpiride (at 1 and 4 mu g/0.5 mu l/NAc) or SCH-23390 (at 0.25, 1 and 4 mu g/0.5 mu l/NAc) prior to FSS and morphine disrupts the antinociceptive effects of morphine and morphine sensitization. Our findings suggest that FSS can potentiate the effect of morphine and causes morphine sensitization which induces antinociception. (C) 2016 Elsevier Inc. All rights reserved.