Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.
Abstract
We studied the effect of opiates acting preferentially on mu receptors, like morphine, methadone and fentanyl (mu agonists) and on kappa receptors, like U50,488, bremazocine and tifluadom (kappa agonists) on the release of dopamine (DA) and of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, from the nucleus accumbens and from the dorsal caudate of freely moving rats using brain dialysis coupled to high-performance liquid chromatography with electrochemical detection. Spontaneous behavior was videotaped and analyzed by estimating the percentage of time spent by the animals in performing certain specific behavioral items. Mu agonists stimulated DA-release and metabolism in the accumbens at lower doses than in the caudate. Maximal stimulation of DA release did not exceed 100% except after high doses of methadone (10 mg/kg) which stimulated DA release in the accumbens by more than 300%, possibly as a result of hypoxia. Stimulation of DA release was associated to stimulation of behavior at low doses and to a biphasic inhibitory-stimulatory syndrome after higher doses of the opiates. Pretreatment with low doses of naloxone (0.1 mg/kg s.c.) or with the irreversible mu antagonist beta-funaltrexamine (10 nmol i.c.v.) increased the ED50 for the stimulation of DA release by the three opiates. In contrast with mu agonists, agonists of kappa receptors like U50,488, bremazocine and tifluadom decreased DA release in the accumbens and in the caudate and reduced motor activity. These effects were antagonized only by rather high doses of naloxone (2.5 mg/kg s.c.) and were not affected by pretreatment with beta-funaltrexamine (10 nmol i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
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Opioids interact with other addiction-related neurochemical systems, including dopamine and glutamate, though these interactions do not entirely explain the role of opioids in addiction.
“Opioids also interact with other addiction-related neurochemical systems, including DA and glutamate, though these interactions do not entirely explain the role of opioids in addiction (Dichiara and Imperato 1988; Johnson and North 1992; Scavone et al 2011).”
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- Authors
- Di Chiara, G., & Imperato, A.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1988-03
- Volume
- 244
- Issue
- 3
- Pages
- 1067-1080
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1958969306
- Cited by
- 916
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 18 · 2020: 16 · 2019: 25 · 2018: 23 · 2017: 18 · 2016: 25 · 2015: 19 · 2014: 25 · 2013: 29 · 2012: 23
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mu-opioid receptor agonists, kappa opioid receptor agonists, dopamine release, nucleus accumbens, dorsal caudate, morphine, methadone, fentanyl, U50,488, bremazocine, tifluadom, dihydroxyphenylacetic acid, homovanillic acid, naloxone, beta-funaltrexamine, motor activity, opioid dose-response, freely moving rats
- MeSH terms
- Animals, Benzomorphans, Caudate Nucleus, Dopamine, Male, Methadone, Morphine, Motor Activity, Naloxone, Naltrexone, Nucleus Accumbens, Rats, Inbred Strains, Receptors, Opioid, Reward, Septal Nuclei, Receptors, Opioid, mu, Receptors, Opioid, kappa, Rats
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