Opioids excite dopamine neurons by hyperpolarization of local interneurons

Johnson, SW; North, RA

doi:10.1523/jneurosci.12-02-00483.1992

Cited by 1,637Neurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal PhysiologyNeuroscience and Neuropharmacology Research

Opioids excite dopamine neurons by hyperpolarization of local interneurons

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Johnson, SW, North, RA·1992·The Journal of Neuroscience

DOI 10.1523/jneurosci.12-02-00483.1992PMC PMC6575608

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Abstract

Increased activity of dopamine-containing neurons in the ventral tegmental area is necessary for the reinforcing effects of opioids and other abused drugs. Intracellular recordings from these cells in slices of rat brain in vitro showed that opioids do not affect the principal (dopamine-containing) neurons but hyperpolarize secondary (GABA- containing) interneurons. Experiments with agonists and antagonists selective for opioid receptor subtypes indicated that the hyperpolarization of secondary cells involved the mu-receptor. Most principal cells showed spontaneous bicuculline-sensitive synaptic potentials when the extracellular potassium concentration was increased from 2.5 to 6.5 or 10.5 mM; these were prevented by TTX and assumed to result from action potentials arising in slightly depolarized local interneurons. The frequency of these synaptic potentials, but not their amplitudes, was reduced by opioids selective for mu-receptors. It is concluded that hyperpolarization of the interneurons by opioids reduces the spontaneous GABA-mediated synaptic input to the dopamine cells. In vivo, this would lead to excitation of the dopamine cells by disinhibition, which would be expected to contribute to the positive reinforcement seen with mu-receptor agonists such as morphine and heroin.

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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).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Johnson and North 1992
Opiate administration appears to inhibit ventral tegmental GABAergic neurons, which tonically inhibit dopaminergic neurons, thus removing tonic inhibition over dopamine neurons and activating dopamine neurons.
“Opiate administration appears to inhibit ventral tegmental GABAergic neurons, which tonically inhibit dopaminergic neurons, thus removing tonic inhibition over dopamine neurons and, in turn, activating dopamine neurons (Gysling and Wang, 1983; Johnson and North, 1992).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Johnson and North, 1992
The reinforcing effects of opiates administered into the VTA are thought to be mediated via local GABAergic neurons.
“The reinforcing effects of opiates administered into the VTA are thought to be mediated via local GABAergic neurons.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Johnson and North, 1992
Administration of opiates, systemically or locally, appears to disinhibit dopaminergic neurons in the VTA.
“Administration of opiates, systemically or locally, appears to disinhibit dopaminergic neurons in the VTA (Gysling and Wang, 1983; Matthews and German, 1984; Johnson and North, 1992).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Johnson and North, 1992

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Authors: Johnson, S., & North, R.
Affiliations: Oregon Health & Science University (US)
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1992-02-01
Volume: 12
Issue: 2
Pages: 483-488
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.12-02-00483.1992
PMC: PMC6575608
OpenAlex: W2169863475
Cited by: 1,637
References: 40
Citations by year: 2026: 37 · 2025: 47 · 2024: 48 · 2023: 47 · 2022: 55 · 2021: 54 · 2020: 62 · 2019: 60 · 2018: 61 · 2017: 51 · 2016: 76 · 2015: 55 · 2014: 71 · 2013: 54 · 2012: 77
FWCI: 9.65
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Health and Human Services
National Institutes of Health (5r01mh040416-17, 5k08ns001423-05, 5r01da003161-12)
National Institute of Mental Health (MH 40416)
National Institute on Drug Abuse (DA03161)
National Institute of Neurological Disorders and Stroke (NS01423)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: opioids, dopaminergic neurons, ventral tegmental area, local interneurons, GABAergic interneurons, mu-opioid receptor, disinhibition, synaptic inhibition, opioid reinforcement, morphine, heroin
MeSH terms: Analgesics, Opioid, Animals, Bicuculline, Dopamine, Enkephalin, Methionine, Enkephalins, Evoked Potentials, gamma-Aminobutyric Acid, Interneurons, Male, Membrane Potentials, Mesencephalon, Neurons, Pyrrolidines, Rats, Inbred Strains, Receptors, GABA-A, Synapses, 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Enkephalin, D-Penicillamine (2,5)-, Rats, In Vitro Techniques

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