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Rewarding and Psychomotor Stimulant Effects of Endomorphin-1: Anteroposterior Differences within the Ventral Tegmental Area and Lack of Effect in Nucleus Accumbens
Open accessAbstract
Endomorphin-1 (EM-1) is a recently isolated endogenous peptide having potent analgesic activity and high affinity and selectivity for the mu-opioid receptor. The present study was designed to investigate the rewarding and psychomotor stimulant effects of EM-1 in specific brain regions. We found that rats would learn without priming or response shaping to lever-press for microinjections of EM-1 into the ventral tegmental area (VTA); responding was most vigorous for high-dose injections into the posterior VTA. Rats did not learn to lever-press for microinjections of EM-1 into the nucleus accumbens (NAS) or regions just dorsal to the VTA. Lever-pressing for EM-1 in the VTA was extinguished when vehicle was substituted for the peptide and was reinstated when EM-1 reinforcement was re-established. Conditioned place preference was established by EM-1 injections into the posterior but not the anterior VTA or the NAS. Injection of EM-1 (0.1-1.0 nmol) into the posterior VTA induced robust increases in locomotor activity, whereas injections into the anterior VTA had very weak locomotor-stimulating effects. When injected into the NAS, EM-1 (0.1-10.0 nmol) did not affect locomotor activity. The present findings implicate the posterior VTA as a highly specific and sensitive site for opioid reward and suggest a role for EM-1-containing projections to the posterior VTA in the rewarding effects of other reinforcers.
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“Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zangen et al., 2002
Experimental — accuracy not yet measuredIn the citing paper
“Rats learn to lever-press for administration of drugs such as nicotine (Ikemoto et al., 2006), carbachol (Ikemoto and Wise, 2002), opiates (Zangen et al., 2002), cannabinoids (Zangen et al., 2006), cocaine (Rodd et al., 2005), ethanol (Rodd-Henricks et al., 2000) and its metabolite acetaldehyde (Rodd et al., 2004) into the posterior VTA more readily than into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zangen et al., 2002
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“Other drugs of abuse such as nicotine and opiates appear to act in the posteromedial VTA and central linear nucleus.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zangen et al., 2002
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Citations
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Cited by
Sorted by citations
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Tzschentke, T. M. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00070.x · Cited by 1,336
Reward Processing by the Opioid System in the Brain
Le Merrer, J., Becker, J. A. J., Befort, K., & Kieffer, B. L. (2009) · Physiological Reviews · doi:10.1152/physrev.00005.2009 · Cited by 1,013
Wise, R. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00965-0 · Cited by 881
Jhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.001 · Cited by 696
Metadata
- Authors
- Zangen, A., Ikemoto, S., Zadina, J. E., & Wise, R. A.
- Affiliations
- National Institutes of Health (US)
- Tulane University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-15
- Volume
- 22
- Issue
- 16
- Pages
- 7225-7233
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757872
- OpenAlex
- W1888155279
- Cited by
- 138
- References
- 47
- Citations by year
- 2026: 4 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 11
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse
- 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 › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- endomorphin-1, opioid reward, ventral tegmental area, nucleus accumbens, mu-opioid receptor, conditioned place preference, locomotor activity, reinstatement, opioid analgesia
- MeSH terms
- Animals, Behavior, Animal, Choice Behavior, Dose-Response Relationship, Drug, Drug Administration Routes, Male, Microinjections, Motor Activity, Nucleus Accumbens, Oligopeptides, Reinforcement, Psychology, Reward, Self Administration, Spatial Behavior, Rats, Sprague-Dawley, Receptors, Opioid, mu, Ventral Tegmental Area, Rats
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