Cocaine reward and hyperactivity in the rat: Sites of mu opioid receptor modulation
Open accessAbstract
Opioid receptor agonists and antagonists have profound effects on cocaine-induced hyperactivity and conditioned reward. Recently, the role specifically of the mu opioid receptor has been demonstrated based on the finding that i.c.v. administration of the selective mu opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), can attenuate cocaine-induced behaviors. The purpose of the present study was to determine the location of mu opioid receptors that are critical for cocaine-induced reward and hyperactivity. Adult male Sprague-Dawley rats received injections of CTAP into the caudate putamen, the rostral or caudal ventral tegmental area (VTA) or the medial shell or core of the nucleus accumbens prior to cocaine to determine the role of mu opioid receptors in cocaine-induced reward and hyperactivity. Cocaine-induced reward was assessed using an unbiased conditioned place preference procedure. Results demonstrate that animals pre-treated with CTAP into the nucleus accumbens core or rostral VTA, but not the caudal VTA, caudate putamen or medial nucleus accumbens shell, during conditioning with cocaine showed an attenuation of the development of cocaine-induced place preference. In contrast, CTAP injected into the nucleus accumbens shell but not the core attenuated the expression of cocaine place preference. Intra-nucleus accumbens core, caudate putamen or caudal VTA CTAP significantly attenuated cocaine-induced hyperactivity. In addition, the number of cFos positive cells was increased in the motor cortex, medial and ventromedial aspects of the nucleus accumbens shell, basolateral amygdala and caudal VTA during the expression of cocaine place preference, and this increase was attenuated in the animals that received intra-accumbens core CTAP during daily cocaine conditioning. These results demonstrate the importance of mu opioid receptors in the nucleus accumbens and VTA in cocaine-induced reward and hyperactivity and suggest that some aspects of the behavioral effects of cocaine are mediated by endogenous activation of mu opioid receptors in these brain regions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The rewarding or reinforcing value of many drugs of abuse can be blocked by MOR antagonists injected into the nucleus accumbens, ventral pallidum, or VTA.
“Similarly, the rewarding or reinforcing value of many drugs of abuse can be blocked by MOR antagonists injected into the NAC, the VP, or the VTA (Hiroi and White 1993; Skoubis and Maidment 2003; Soderman and Unterwald 2008).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Soderman and Unterwald 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Alexander, G. E., Crutcher, M. D., & DeLong, M. R. (1990) · PubMed · Cited by 2,422 · see citing works
Cocaine Receptors on Dopamine Transporters Are Related to Self-Administration of Cocaine
Ritz, M. C., Lamb, R. J., Goldberg, S. R., & Kuhar, M. J. (1987) · Science · doi:10.1126/science.2820058 · Cited by 2,180 · see citing works
(1991) · Progress in Brain Research · doi:10.1016/s0079-6123(08)62678-3 · Cited by 1,961 · see citing works
Opioids excite dopamine neurons by hyperpolarization of local interneurons
Johnson, S., & North, R. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00483.1992 · Cited by 1,637 · see citing works
Specificity in the projection patterns of accumbal core and shell in the rat
Heimer, L., Zahm, D. S., Churchill, L., Kalivas, P. W., & Wohltmann, C. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90202-y · Cited by 1,219 · see citing works
Pontieri, F. E., Tanda, G., & Chiara, G. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.12304 · Cited by 868 · see citing works
Two types of neurone in the rat ventral tegmental area and their synaptic inputs.
Johnson, S. W., & NORTH, R. A. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019136 · Cited by 672 · see citing works
Roberts, D. C. S., & Koob, G. F. (1982) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(82)90469-5 · Cited by 448 · see citing works
Neisewander, J. L., Baker, D. L., Fuchs, R. A., Tran-Nguyen, L. T. L., Palmer, A., & Marshall, J. F. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-02-00798.2000 · Cited by 432 · see citing works
The accumbens: beyond the core-shell dichotomy
Heimer, L., Alheid, G. F., de Olmos, J. S., Groenewegen, H. J., Haber, S. N., Harlan, R. E., & Zahm, D. S. (1997) · Journal of Neuropsychiatry · doi:10.1176/jnp.9.3.354 · Cited by 418 · see citing works
Two transpallidal pathways originating in the rat nucleus accumbens
Zahm, D. S., & Heimer, L. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903020302 · Cited by 406 · see citing works
Tempel, A., & Zukin, R. S. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.12.4308 · Cited by 383 · see citing works
Pettit, H. O., & Justice, J. B. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90291-8 · Cited by 375 · see citing works
Joyce, E. M., & Iversen, S. D. (1979) · Neuroscience Letters · doi:10.1016/0304-3940(79)96149-4 · Cited by 356 · see citing works
Kalivas, P. W., Churchill, L., & Klitenick, M. A. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90048-k · Cited by 353 · see citing works
Neural systems for behavioral activation and reward
Kalivas, P. W., & Nakamura, M. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80031-2 · Cited by 335 · see citing works
Molecular alterations in the neostriatum of human cocaine addicts
Hurd, Y. L., & Herkenham, M. A. (1993) · Synapse · doi:10.1002/syn.890130408 · Cited by 316 · see citing works
Olive, M. F., Koenig, H. N., Nannini, M., & Hodge, C. W. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-23-j0002.2001 · Cited by 300 · see citing works
Brown, E., Robertson, G. S., & Fibiger, H. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-10-04112.1992 · Cited by 288 · see citing works
Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of rats
Devine, D. P., & Wise, R. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-01978.1994 · Cited by 256 · see citing works
Sellings, L. H. L., & Clarke, P. B. S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06295.2003 · Cited by 231 · see citing works
Olmstead, M. C., & Franklin, K. B. J. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.6.1324 · Cited by 231 · see citing works
Repeated cocaine administration upregulates K and μ, but not δ, opioid receptors
Unterwald, E. M., Rubenfeld, J. M., & Kreek, M. J. (1994) · Neuroreport · doi:10.1097/00001756-199408150-00018 · Cited by 230 · see citing works
Self-citationHeikkila, R. E., Orlansky, H., Mytilineou, C., & Cohen, G. (1975) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)30227-2 · Cited by 220 · see citing works
Olmstead, M. C., & Franklin, K. B. J. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.6.1324 · Cited by 216 · see citing works
Cocaine induced secretion of ACTH, beta-endorphin, and corticosterone
Moldow, R. L., & Fischman, A. J. (1987) · Peptides · doi:10.1016/0196-9781(87)90065-9 · Cited by 212 · see citing works
Fink, J. S., & Smith, G. P. (1980) · Brain Research · doi:10.1016/0006-8993(80)90695-2 · Cited by 210 · see citing works
Zahm, D. S., Záborszky, L., Alones, V., & Heimer, L. (1985) · Brain Research · doi:10.1016/0006-8993(85)90331-2 · Cited by 196 · see citing works
Hooks, M. S., Colvin, A. C., Juncos, J. L., & Justice, J. B. (1992) · Brain Research · doi:10.1016/0006-8993(92)91012-4 · Cited by 192 · see citing works
Comparison of the distribution of D-1 and D-2 dopamine receptors in the rat brain.
Wamsley, J. K., Gehlert, D. R., Filloux, F. M., & Dawson, T. M. (1989) · PubMed · Cited by 168 · see citing works
Opiate antagonists reduce cocaine but not nicotine self-administration
Corrigall, W. A., & Coen, K. M. (1991) · Psychopharmacology · doi:10.1007/bf02244173 · Cited by 156 · see citing works
Ikemoto, S., Kohl, R. R., & McBride, W. J. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010137.x · Cited by 155 · see citing works
Tang, X., McFarland, K., Cagle, S., & Kalivas, P. W. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0685-05.2005 · Cited by 148 · see citing works
Crawford, C. A., McDougall, S. A., Bolaños, C. A., Hall, S. E., & Berger, S. P. (1995) · Psychopharmacology · doi:10.1007/bf02245810 · Cited by 130 · see citing works
Ikemoto, S., Murphy, J. M., & McBride, W. J. H. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.2.369 · Cited by 117 · see citing works
Cocaine alters opiate receptor binding in critical brain reward regions
Hammer, R. P. (1989) · Synapse · doi:10.1002/syn.890030108 · Cited by 106 · see citing works
Naloxone attenuation of the effect of cocaine on rewarding brain stimulation
Bain, G. T., & Kornetsky, C. H. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90575-3 · Cited by 104 · see citing works
Altered Prelimbic Cortex Output during Cue-Elicited Drug Seeking
Miller, C. A., & Marshall, J. F. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1685-04.2004 · Cited by 102 · see citing works
Self-infusion of GABAA antagonists directly into the ventral tegmental area and adjacent regions.
Ikemoto, S., Murphy, J. M., & McBride, W. J. H. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.2.369 · Cited by 102 · see citing works
Opioid mediation of cocaine-induced hyperactivity and reinforcement
Houdi, A. A., Bardo, M. T., & Loon, G. R. V. (1989) · Brain Research · doi:10.1016/0006-8993(89)90989-x · Cited by 101 · see citing works
Roth‐Deri, I., Zangen, A., Aleli, M., Goelman, R. G., Pelled, G., Nakash, R., Gispan-Herman, I., Green, T., Shaham, Y., & Yadid, G. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01584.x · Cited by 94 · see citing works
Hauber, W., & Münkle, M. C. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)00040-x · Cited by 89 · see citing works
Opioidergic modulation of cocaine conditioned place preferences
Bilsky, E. J., Montegut, M. J., Delong, C. L., & Reid, L. D. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90105-x · Cited by 83 · see citing works
Mathon, D. S., Lesscher, H. M. B., Gerrits, M. A. F. M., Kamal, A., Pintar, J. E., Schuller, A. G., Spruijt, B. M., Burbach, J. P. H., Smidt, M. P., van Ree, J. M., et al. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.10.002 · Cited by 55 · see citing works
Skoubis, P. D., & Maidment, N. T. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00121-0 · Cited by 54 · see citing works
Izenwasser, S., Heller, B., & Cox, B. M. (1996) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00828-4 · Cited by 46 · see citing works
Nicolaysen, L. C., & Justice, J. B. (1988) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(88)90354-1 · Cited by 43 · see citing works
Ramsey, N. F., Gerrits, M. A. F. M., & van Ree, J. M. (1999) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(98)00009-1 · Cited by 41 · see citing works
Schroeder, J. A., Niculescu, M., & Unterwald, E. M. (2002) · Synapse · doi:10.1002/syn.10148 · Cited by 39 · see citing works
Self-citationKim, H.-S., Park, W., Jang, C., Oh, K., Kong, J., Oh, S., Rheu, H.-M., Cho, D. H., & Kang, S.-Y. (1997) · Behavioural Brain Research · doi:10.1016/s0166-4328(96)00162-3 · Cited by 29 · see citing works
A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat
Schroeder, J. A., Hummel, M., Simpson, A. D., Sheikh, R., Soderman, A. R., & Unterwald, E. M. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0883-z · Cited by 29 · see citing works
Self-citationLack of morphine-induced hyperactivity in C57BL/6 mice following striatal kainic acid lesions
Siegfried, B., Filibeck, U., Gozzo, S., et al. (1982) · Behavioural Brain Research · doi:10.1016/0166-4328(82)90063-8 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Navratilova, E., Xie, J. Y., Okun, A., Qu, C., Eyde, N., Ci, S., Ossipov, M. H., King, T., Fields, H. L., & Porreca, F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214605109 · Cited by 313 · see citing works
Burkett, J. P., & Young, L. J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2794-x · Cited by 307 · see citing works
“Similarly , lesions that disrupt the release of DA from the VTA into the NAC , or simultaneous antagonism of D1R and D2R in the NAC , all disrupt motivated maternal behaviors such as retrieval without disrupting passive maternal behaviors such as nursing ( Gaffori and Le Moal 1979 ; Hansen et al .”
InfluentialMindfulness-based Group Therapy for Women with Provoked Vestibulodynia
Brotto, L. A., Basson, R., Smith, K. B., Driscoll, M., & Sadownik, L. (2015) · Mindfulness · doi:10.1007/s12671-013-0273-z · Cited by 131 · see citing works
Shi, X., Miller, J. S., Harper, L. J., Poole, R. L., Gould, T. J., & Unterwald, E. M. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3491-8 · Cited by 79 · see citing works
Self-citation
- Authors
- Soderman, A. R., & Unterwald, E. M.
- Affiliations
- Temple University (US)
- Rockefeller University (US)
- ORCID
- Unterwald, E.M.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 154
- Issue
- 4
- Pages
- 1506-1516
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2585317
- OpenAlex
- W1992341451
- Cited by
- 71
- References
- 54
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 3 · 2012: 14
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P30DA013429, R01 DA09580, R01DA009580)
- 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
- cocaine, mu-opioid receptor, cocaine reward, cocaine-induced hyperactivity, conditioned place preference, nucleus accumbens, ventral tegmental area, caudate-putamen, CTAP, c-fos, nucleus accumbens shell, nucleus accumbens core
- MeSH terms
- Animals, Cocaine, Conditioning, Operant, Immunohistochemistry, Injections, Intraventricular, Male, Nucleus Accumbens, Peptide Fragments, Psychomotor Agitation, Reward, Somatostatin, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Receptors, Opioid, mu, Ventral Tegmental Area, Dopamine Uptake Inhibitors, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
