The Effects of Opioid Peptides on Dopamine Release in the Nucleus Accumbens: An In Vivo Microdialysis Study
Abstract
Abstract: An involvement of the mesolimbic dopamine (DA) system in mediating the motivational effects of opioids has been suggested. Accordingly, the present study employed the technique of in vivo microdialysis to examine the effects of selective μ‐, δ‐, and k‐ opioids on DA release in the nucleus accumbens (NAC) of anesthetized rats. Microdialysis probes were inserted into the NAC and perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid (DO‐PAC) and homovanillic acid (HVA), using a reverse‐phase HPLC system with electrochemical detection for separation and quantification. Intracerebroventricular (i.c.v.) administration of selective μ‐opioid [D‐Ala2, N‐methyl‐Phe4, Gly 5‐ol]‐enkephalin (DAMGO) or δ‐opioid [d‐Pen2, d‐Pen 5]‐en‐kephalin (DPDPE) agonists, at doses that function as positive reinforcers in rats, resulted in an immediate and significant increase in extracellular DA. DOPAC and HVA levels were also significantly increased. The effects of DAMGO were blocked by the selective μ‐antagonist d‐Pen‐Cys‐Tyr‐d‐Trp‐Orn‐Thr‐Pen‐Thr‐NH 2 (CTOP) whereas those of DPDPE were blocked by the δ‐antagonist allyl 2‐Tyr‐Aib‐Aib‐Phe‐Leu‐OH (ICI 174,864). In contrast to μ‐ and δ‐agonists, the k‐agonist N‐CH 3‐Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐N‐CH 3‐Arg‐d‐Leu‐NHC 2 H 5 (E‐2078). a dynorphin analog that produces aversive states, decreased DA release in a biphasic manner. Norbin‐altorphimine, a selective k‐antagonist, could block this effect. These results demonstrate that μ‐, δ‐, and k‐opioid agonists differentially affect DA release in the NAC and this action is centrally mediated.
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Drugs of abuse cause dynorphin release and up-regulation of dynorphin in the dorsal and ventral striatum, which inhibits dopamine release by acting on KOR receptors and is therefore thought to be compensatory.
“Drugs of abuse cause dynorphin release and up-regulation of dynorphin in the dorsal and ventral striatum, which inhibits DA release by acting on KOR receptors and is therefore thought to be compensatory (Hanson et al 1988; Sivam 1989; Spanagel et al 1990; Hurd et al 1992; Daunais et al 1993; El Daly et al 2000; Isola et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Spanagel et al 1990
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- Authors
- Spanagel, R., Herz, A., & Shippenberg, T. S.
- Affiliations
- Max Planck Society (DE)
- Corresponding author
- Spanagel, Rainer
- ORCID
- Spanagel, Rainer
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1990-11
- Volume
- 55
- Issue
- 5
- Pages
- 1734-1740
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2040873559
- Cited by
- 539
- References
- 29
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 14 · 2020: 7 · 2019: 12 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 12 · 2014: 16 · 2013: 15 · 2012: 16
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- opioid peptides, dopamine release, nucleus accumbens, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, DAMGO, DPDPE, dynorphin, CTOP, ICI 174,864, nor-binaltorphimine, mesolimbic dopamine system, positive reinforcement, aversive effects, DOPAC, homovanillic acid
- MeSH terms
- Analgesics, Animals, Dialysis, Dopamine, Dynorphins, Endorphins, Enkephalins, Injections, Intraventricular, Magnesium, Male, Nucleus Accumbens, Peptide Fragments, Potassium, Rats, Inbred Strains, Tetrodotoxin, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Enkephalin, D-Penicillamine (2,5)-, Rats
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