Mu opioid receptor mRNA in nucleus accumbens is elevated following dopamine receptor activation

Neurochem Res. 1996 Nov;21(11):1411-5. doi: 10.1007/BF02532382.


We have previously demonstrated that continuous cocaine treatment for three days induces a marked but transient increase in mu opioid receptor (MOR) mRNA in nucleus accumbens (n. acc.); SCH 23390 and eticlopride, selective antagonists of D1- and D2-like dopamine (DA) receptors, respectively, blocked this cocaine-induced upregulation of MOR mRNA in n. acc. suggesting involvement of both subfamilies of DA receptors in the effect of cocaine (1,2). In the present study the ability of the selective DA D3 receptor antagonist, nafadotride (3,4), to prevent the cocaine-induced upregulation of MOR mRNA in n. acc. has been examined. Also, regulation of MOR mRNA following chronic administration of the DA agonists, SKF 38393, R(+)-6-Bromo-APB hydrobromide, or bromocriptine, has been studied. Male Sprague-Dawley rats were treated for 3 days with saline, cocaine, the DA receptor agonists or antagonist delivered by osmotic minipump. Expression of MOR mRNA in n. acc. was estimated by quantitative competitive polymerase chain reaction (PCR) assays following reverse transcription. Nafadotride (1.0 mg/kg/day) prevented the cocaine-induced upregulation of MOR mRNA in n. acc. When administered alone, nafadotride did not change the expression of MOR mRNA. The levels of MOR mRNA were elevated in n. acc. after 3 days treatment with each of the DA agonists, SKF 38393 (4.0 mg/kg/day), R(+)-6-Bromo-APB hydrobromide (4.0 mg/kg/day), or bromocriptine (5.0 mg/kg/day). Thus, DA agonists mimick the effect of cocaine on the expression of MOR mRNA in n. acc. These data confirm the involvement of dopaminergic mechanisms in the mediation of cocaine effects, indicate the comparability of actions of indirect and direct DA agonists, and point to the usefulness of cocaine as a tool to expose interaction between dopaminergic and opioid systems. The results suggest that activation of more than one type of DA receptor is required for the increased expression of MOR mRNA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Bromocriptine / pharmacology
  • Cocaine / pharmacology
  • Dopamine Antagonists / pharmacology*
  • Male
  • Naphthalenes / pharmacology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Pyrrolidines / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / physiology
  • Receptors, Dopamine D2 / physiology
  • Receptors, Dopamine D3
  • Receptors, Opioid, mu / biosynthesis*
  • Salicylamides / pharmacology*
  • Transcription, Genetic / drug effects
  • Up-Regulation / drug effects*


  • Benzazepines
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Naphthalenes
  • Pyrrolidines
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Opioid, mu
  • Salicylamides
  • Bromocriptine
  • Cocaine
  • eticlopride
  • nafadotride