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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.
Naunyn Schmiedebergs Arch Pharmacol. 1997 May; 355(5):582-8.NS

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.

Authors+Show Affiliations

Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, (Monash University), Parkville, Australia.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9151296

Citation

Borg, P J., and D A. Taylor. "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." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 355, no. 5, 1997, pp. 582-8.
Borg PJ, Taylor DA. 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. Naunyn Schmiedebergs Arch Pharmacol. 1997;355(5):582-8.
Borg, P. J., & Taylor, D. A. (1997). 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. Naunyn-Schmiedeberg's Archives of Pharmacology, 355(5), 582-8.
Borg PJ, Taylor DA. 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. Naunyn Schmiedebergs Arch Pharmacol. 1997;355(5):582-8. PubMed PMID: 9151296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Borg,P J, AU - Taylor,D A, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 582 EP - 8 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 355 IS - 5 N2 - 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. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/9151296/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_ DB - PRIME DP - Unbound Medicine ER -