The role of dopamine in intracranial self-stimulation of the ventral tegmental area
Open accessAbstract
The role of dopaminergic (DA) neurons in brain stimulation reward produced by electrical stimulation of the ventral tegmental area (VTA) was investigated in the rat. In the first experiment, extensive 6- hydroxydopamine lesions of the ascending fibers of the mesotelencephalic DA projections resulted in significant changes in intracranial self-stimulation (ICS) rate-current intensity functions when the lesion was ipsilateral to the stimulating electrode. Similar contralateral lesions had no effect on these functions, thus ruling out lesion-induced performance deficits as being responsible for the decreases in ICS rates across the wide range of current intensities that occurred after the ipsilateral lesions. In the second experiment, ICS obtained from electrodes in the VTA resulted in significant increases in the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, nucleus accumbens, and olfactory tubercle ipsilateral to the stimulating electrode. The ratios of DOPAC and HVA to DA, considered to be indices of DA utilization, were also increased in these brain regions ipsilateral to the electrode. No changes were observed in the contralateral striatum, nucleus accumbens, and olfactory tubercle. Similar increases were observed in stimulated “yoked” animals that received brain stimulation at identical rates and currents but did not lever-press for this stimulation. The third experiment examined the effects of lever- pressing for food on an FR8 schedule of reinforcement on DA utilization in the striatum, nucleus accumbens, and olfactory tubercle. Despite high rates of responding, no effects were observed on DOPAC:DA or HVA:DA ratios in these brain regions.
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The crucial mechanism for the development of addiction is drug-induced activation of DA transmission in the mesolimbic pathway (the 'dopamine hypothesis of addiction').
“It has been proposed that the crucial mechanism for the development of addiction is drug-induced activation of DA transmission in the mesolimbic pathway, also referred to as the ‘dopamine hypothesis of addiction’ [121-123].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [121]
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- Authors
- Fibiger, H., LePiane, F., Jakubovic, A., & Phillips, A.
- Affiliations
- University of British Columbia (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1987-12-01
- Volume
- 7
- Issue
- 12
- Pages
- 3888-3896
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6569118
- OpenAlex
- W1669836444
- Cited by
- 189
- References
- 32
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2022: 6 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 5
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council Canada
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- dopamine, ventral tegmental area, intracranial self-stimulation, brain stimulation reward, 6-hydroxydopamine lesion, DOPAC, homovanillic acid, dopamine utilization, striatum, nucleus accumbens, olfactory tubercle, food reinforcement, lever pressing
- MeSH terms
- Animals, Brain Diseases, Corpus Striatum, Dopamine, Electric Stimulation, Homovanillic Acid, Hydroxydopamines, Male, Nucleus Accumbens, Olfactory Bulb, Reinforcement, Psychology, Tegmentum Mesencephali, 3,4-Dihydroxyphenylacetic Acid, Oxidopamine, Rats
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