Chronic repeated cocaine administration alters basal and opioid‐regulated adenylyl cyclase activity

Ellen M. Unterwald, Brian M. Cox, Mary Jeanne Kreek, Thomas E. Cote, Sari Izenwasser

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Repeated daily cocaine injections have been shown to alter μ-opioid receptor densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et al., 1991, 1992). Adenylyl cyclase activity was measured in rat rostral caudate putamen and nucleus accumbens following repeated cocaine administration to determine the functional consequences of cocaine-induced opioid receptor changes. Male Fischer rats were injected daily for 14 days with saline or cocaine HCl (30 or 45 mg/kg/day, i.p.) in three equal doses at 1-hr intervals. Basal adenylyl cyclase activity and the effects of the selective μ- and δ-opioid agonists [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) and [D-penicillamine2,D-Penicillamine5]enkephalin (DPDPE), respectively, on adenylyl cyclase activity were examined 30 min after the last injection using a cAMP radioligand binding assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and 34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of cocaine, respectively, as compared to those receiving saline injections. Basal adenylyl cyclase activity was unchanged in the nucleus accumbens following cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and 30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus accumbens of saline-injected animals. Administration of cocaine attenuated the ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase activity. These results suggest that chronic, repeated cocaine administration results in a selective impairment of δ-opioid receptor-mediated effector function in the caudate putamen and nucleus accumbens.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalSynapse
Volume15
Issue number1
DOIs
StatePublished - Sep 1993
Externally publishedYes

Keywords

  • Caudate putamen
  • DAMGO
  • DPDPE
  • Delta opioid
  • Dopamine
  • Mu opioid
  • Nucleus accumbens
  • Rat brain

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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