Involvement of mu- and delta-opioid receptors in the effects of systemic and locally perfused morphine on extracellular levels of dopamine, DOPAC and HVA in the nucleus accumbens of the halothane-anaesthetized rat.

Abstract

The effects of systemic and intra-accumbens infusion of morphine on the extracellular level of dopamine (DA) and its metabolites, DOPAC and HVA, were investigated in the nucleus accumbens (NAcc) of halothane-anaesthetized rats using in vivo microdialysis. Morphine in a dose of 1 or 5 mg/kg i.v. produced a significant increase (60-100% of baseline levels) in the extracellular level of DA for at least 3 h. Morphine at 5, but not 1 mg/kg, produced a small (10-15%) but significant reduction in the level of DOPAC when compared with saline in the first h following injection. Pretreatment with the preferential mu-opioid receptor antagonist naloxone in a dose of 1 or 3 mg/kg i.p. significantly blocked the morphine-induced changes in the extracellular levels of DA and DOPAC. Pretreatment with the selective delta-opioid receptor antagonist, naltrindole, at 1 mg/kg i.p. blocked only the morphine-induced decrease in DA metabolism. Furthermore, in the presence of naltrindole, systemic morphine induced a large and long-lasting increase in the level of DOPAC and HVA, which was significantly higher than in rats receiving combinations of saline/water + saline, saline/water + morphine and naltrindole + saline. When applied directly into the NAcc, morphine at concentrations of 125, 250 and 500 ng infused over 10 min produced a dose-related increase in the extracellular level of accumbens DA with either no effect or a small reduction in the level of DOPAC and HVA. The effects of intra-accumbens morphine on DA levels were significantly blocked by pretreatment with i.p. naltrindole but not naloxone. These results indicate that, while systemic morphine probably increases DA via activation of mu-opioid receptors, local perfusion of morphine increases DA in the NAcc via activation of delta-opioid receptors located in the NAcc. Furthermore, under the conditions of the study, it appears that activation of mu- and delta-opioid receptors by morphine respectively increases and decreases DA metabolism.