Morphine withdrawal aggression: modification with D1 and D2 receptor agonists
Abstract
Morphine withdrawal increases aggressive behaviors, induces explosive motor behaviors, and disrupts homeostatic functions in mice and rats. While many of these effects appear to result from altered dopaminergic activity during morphine withdrawal, the relative contributions of the D1 and D2 receptor subtypes remain unclear. In the present experiments, the D1 agonist SKF 38393 and the D2 agonist quinpirole were administered to male "resident" Swiss-Webster mice 5 h after the removal of a subcutaneously-implanted morphine or placebo pellet. These mice were then observed alone to determine changes in various motor activities and in confrontation with a group-housed male "intruder" to assess changes in aggressive behaviors. SKF 38393 decreased the display of aggressive behaviors by placebo and morphine-withdrawn mice without consistently altering walking or rearing. Quinpirole greatly decreased the display of aggressive behaviors by placebo mice and decreased aggressive behaviors in morphine-withdrawn mice to a lesser degree. The inhibitory effects of quinpirole were not specific to aggressive behaviors; low quinpirole doses also decreased the display of walking and rearing. In mice which received a low dose of SKF 38393 preceding quinpirole injection, pretreatment with the D1 agonist did not alter the effects of the D2 agonist quinpirole on motor activities but maintained high levels of aggression in morphine-withdrawn mice. The differential modification of aggressive and motor behaviors by selective dopaminergic agonists during morphine withdrawal further supports the suggestion that aggressive and motor behaviors are controlled independently; furthermore, D1 receptor stimulation appears to have particular relevance for the display of aggressive behaviors during morphine withdrawal.
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The Miczek group has consistently shown heightened aggression during morphine withdrawal in multiple rodent models.
“The Miczek group has consistently shown heightened aggression during morphine withdrawal in multiple rodent models (Kantak and Miczek 1986, 1988; Tidey and Miczek 1992; Vivian and Miczek 1993).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Tidey and Miczek 1992
Cites
Seeman, P. M. (1980) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06839-5 · Cited by 1,888 · see citing works
Di Chiara, G., & Imperato, A. (1988) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24578-5 · Cited by 916 · see citing works
SIMULTANEOUS QUANTITATIVE ASSESSMENT OF MORPHINE TOLERANCE AND PHYSICAL DEPENDENCE
Way, E. L., LOU, H. H., & Shen, F.-H. (1969) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)28317-3 · Cited by 678 · see citing works
Clark, D., & White, F. J. (1987) · Synapse · doi:10.1002/syn.890010408 · Cited by 660 · see citing works
Autoradiographic localization of opiate receptors in rat brain. II. The brain stem
Atweh, S., & Kuhar, M. J. (1977) · Brain Research · doi:10.1016/0006-8993(77)90965-9 · Cited by 567 · see citing works
Spanagel, R., Herz, A., & Shippenberg, T. S. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04963.x · Cited by 539 · see citing works
Bl�sig, J., Herz, A., Reinhold, K., & Zieglg�nsberger, S. (1973) · Psychopharmacology · doi:10.1007/bf00428791 · Cited by 521 · see citing works
Kalivas, P. W., Widerlöv, E., Stanley, D. A., Breese, G. R., & Prange, A. J. (1983) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22000-6 · Cited by 358 · see citing works
Molloy, A. G., & Waddington, J. L. (1984) · Psychopharmacology · doi:10.1007/bf00427697 · Cited by 352 · see citing works
Obligatory D-1/D-2 receptor interaction in the generation of dopamine agonist related behaviors
Braun, A. R., & Chase, T. N. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90588-1 · Cited by 322 · see citing works
Miczek, K. A., & O’Donnell, J. M. (1978) · Psychopharmacology · doi:10.1007/bf00426957 · Cited by 316 · see citing works
Self-citationEnkephalin receptors on dopaminergic neurones in rat striatum
Pollard, H., Llorens‐Cortés, C., & Schwartz, J. (1977) · Nature · doi:10.1038/268745a0 · Cited by 311 · see citing works
Induction of oral dyskinesias in naive rats by D1 stimulation
Rosengarten, H., Schweitzer, J. W., & Friedhoff, A. J. (1983) · Life Sciences · doi:10.1016/0024-3205(83)90155-8 · Cited by 250 · see citing works
Narcotic dependence, narcotic action and dopamine receptors
Lal, H. (1975) · Life Sciences · doi:10.1016/0024-3205(75)90081-8 · Cited by 226 · see citing works
Kelle, A. E., Stinus, L., & Iversen, S. D. (1980) · Behavioural Brain Research · doi:10.1016/0166-4328(80)90043-1 · Cited by 208 · see citing works
Intravenous self-administration of dopamine receptor agonists by rhesus monkeys.
Woolverton, W. L., Goldberg, L. I., & Ginos, J. Z. (1984) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21719-0 · Cited by 204 · see citing works
Arnt, J. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90345-0 · Cited by 200 · see citing works
Stinus, L., Koob, G. F., LING, N. C., Bloom, F. E., & Moal, M. L. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.4.2323 · Cited by 182 · see citing works
White, F. J., Bednarz, L. M., Wachtel, S. R., Hjorth, S., & Brooderson, R. J. (1988) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(88)90442-x · Cited by 177 · see citing works
Motivational effects of opioids: influence of D-1 versus D-2 receptor antagonists
Shippenberg, T. S., & Herz, A. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90803-5 · Cited by 156 · see citing works
Arnt, J., & Hyttel, J. (1985) · Psychopharmacology · doi:10.1007/bf00428200 · Cited by 152 · see citing works
Breese, G. R., Napier, T. C., & Mueller, R. A. (1985) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23467-x · Cited by 149 · see citing works
Spanagel, R., Herz, A., Bals-Kubik, R., & Shippenberg, T. S. (1991) · Psychopharmacology · doi:10.1007/bf02244553 · Cited by 119 · see citing works
Effect of dopaminergic stimulation or blockade on morphine-withdrawal aggression
Puri, S. K., & Lal, H. (1973) · Psychopharmacology · doi:10.1007/bf00428682 · Cited by 119 · see citing works
Arnt, J. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90541-7 · Cited by 95 · see citing works
Ultrasounds during morphine withdrawal in rats
Vivian, J. A., & Miczek, K. A. (1991) · Psychopharmacology · doi:10.1007/bf02244177 · Cited by 84 · see citing works
Self-citationVaccarino, F. J., Amalric, M., Swerdlow, N. R., & Koob, G. F. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90045-6 · Cited by 82 · see citing works
Morphine-withdrawal aggression: Sensitization by amphetamines
Lal, H., O'brien, J., & Puri, S. K. (1971) · Psychopharmacology · doi:10.1007/bf00401783 · Cited by 77 · see citing works
Ethological analysis of drug action on aggression and defense
Miczek, K. A. (1983) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(83)90019-2 · Cited by 55 · see citing works
Self-citationEffects of dopamine depletion on rotational behavior to dopamine agonists
Gershanik, O. S., Heikkila, R. E., & Duvoisin, R. C. (1983) · Brain Research · doi:10.1016/0006-8993(83)90645-5 · Cited by 48 · see citing works
Kantak, K. M., & Miczek, K. A. (1988) · Psychopharmacology · doi:10.1007/bf02180026 · Cited by 46 · see citing works
Self-citationKantak, K., & Miczek, K. (1986) · Psychopharmacology · doi:10.1007/bf00174059 · Cited by 37 · see citing works
Self-citationMaling, H. M., Cohn, V., Highman, B., Williams, M. A., & Thompson, E. C. (1959) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)25689-0 · Cited by 32 · see citing works
Arnt, J. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90098-7 · Cited by 30 · see citing works
Heightened aggressive behavior during morphine withdrawal: effects ofd-amphetamine
Tidey, J. W., & Miczek, K. A. (1992) · Psychopharmacology · doi:10.1007/bf02245151 · Cited by 27 · see citing works
Self-citationEnhancement of morphine-withdrawal and apomorphine-induced aggression by clonidine.
Gianutsos, G., Hynes, & Lal, H. (1976) · PubMed · Cited by 26 · see citing works
The effect of benzodiazepines on the 5-HT agonist-induced head-twitch response in mice
Moser, P. C., & Redfern, P. H. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90802-3 · Cited by 21 · see citing works
The influence of the mode of morphine administration on tolerance and dependence.
Cochin, J., Miller, J. M., Rosow, C. E., Grell, R., & Jl, P. (1979) · PubMed · Cited by 9 · see citing works
Acquas, E., Carboni, E., & Chiara, G. D. (1991) · UNICA IRIS Institutional Research Information System (University of Cagliari) · Cited by 3 · see citing works
Flagged first, then by citations
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Sorted by citations
Gregg, T. R., & Siegel, A. (2001) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(00)00150-0 · Cited by 315 · see citing works
Burkett, J. P., & Young, L. J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2794-x · Cited by 307 · see citing works
“This presents an interesting contrast with literature on other types of aggres - sion in rodents , where both D1R and D2R in the NAC play a role in aggressive behavior and in the motivation to aggress ( Tidey and Miczek 1992a , b ; Rodriguez - Arias et al .”
Escalated aggressive behavior: Dopamine, serotonin and GABA
de Almeida, R. M. M., Ferrari, P. F., Parmigiani, S., & Miczek, K. A. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.10.004 · Cited by 303 · see citing works
Self-citationGobrogge, K. L., Liu, Y., Young, L. J., & Wang, Z. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908620106 · Cited by 178 · see citing works
Miczek, K. A., Weerts, E. M., Haney, M., & Tidey, J. W. (1994) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(94)90040-x · Cited by 154 · see citing works
Self-citationYoung, K. A., Gobrogge, K. L., & Wang, Z. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.06.004 · Cited by 111 · see citing works
Functions of medial hypothalamic and mesolimbic dopamine circuitries in aggression
Yamaguchi, T., & Lin, D. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.06.011 · Cited by 77 · see citing works
Oxycodone self-administration and withdrawal behaviors in male and female Wistar rats
Kimbrough, A., Kononoff, J., Simpson, S., Kallupi, M., Sedighim, S., Palomino, K., Conlisk, D., Momper, J. D., de Guglielmo, G., & George, O. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05479-y · Cited by 62 · see citing works
Radke, A. K., & Gewirtz, J. C. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.97 · Cited by 57 · see citing works
Olson, G. A., Olson, R. D., & Kastin, A. J. (1993) · Peptides · doi:10.1016/0196-9781(93)90195-m · Cited by 55 · see citing works
Monoamines, GABA, Glutamate, and Aggression
Miczek, K. A., & Fish, E. W. (2005) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195168761.003.0005 · Cited by 51 · see citing works
Self-citationNeurochemistry and Molecular Neurobiology of Aggressive Behavior
Miczek, K. A., Faccidomo, S., Fish, E. W., & DeBold, J. F. (2006) · Springer eBooks · doi:10.1007/978-0-387-30405-2_7 · Cited by 45 · see citing works
Self-citationAggression and the Three Opioid Families (Endorphins, Enkephalins, and Dynorphins) in Mice
Tordjman, S., Carlier, M., Cohen, D., Cesselin, F., Bourgoin, S., Colas-Linhart, N., Petiet, A., Pérez-Díaz, F., Hamon, M., & Roubertoux, P. L. (2003) · Behavior Genetics · doi:10.1023/a:1025774716976 · Cited by 40 · see citing works
The dopaminergic system and aggression in laying hens
Dennis, R. L., & Cheng, H. W. (2011) · Poultry Science · doi:10.3382/ps.2011-01513 · Cited by 40 · see citing works
Rodríguez‐Arias, M., Pinazo, J. M., Miñarro, J., & Stinus, L. (1999) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00067-2 · Cited by 38 · see citing works
Sukhotina, I. A., & Bespalov, A. (2000) · Psychopharmacology · doi:10.1007/s002130000386 · Cited by 37 · see citing works
Effect of drugs of abuse on social behaviour
Blanco-Gandía, M. C., Mateos-García, A., García-Pardo, M. P., Montagud‐Romero, S., Rodríguez‐Arias, M., Miñarro, J., & Aguilar, M. A. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000162 · Cited by 35 · see citing works
Diaz, S. L., Kemmling, A. K., Rubio, M. C., & Balerio, G. N. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.10.012 · Cited by 34 · see citing works
Park, Y., Ho, I. K., Fan, L.-W., Loh, H. H., & Ko, K. H. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02001-7 · Cited by 30 · see citing works
Effects of raclopride on aggression and stress in diversely selected chicken lines
Dennis, R. L., Muir, W. M., & Cheng, H. W. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.08.010 · Cited by 28 · see citing works
Schwartzer, J. J., & Melloni, R. H. (2010) · Behavioral Neuroscience · doi:10.1037/a0020899 · Cited by 28 · see citing works
Dopamine, Glutamate, and Aggression
Miczek, K. A., & Fish, E. W. (2005) · Humana Press eBooks · doi:10.1007/978-1-59259-852-6_11 · Cited by 27 · see citing works
Self-citationHeightened aggressive behavior during morphine withdrawal: effects ofd-amphetamine
Tidey, J. W., & Miczek, K. A. (1992) · Psychopharmacology · doi:10.1007/bf02245151 · Cited by 27 · see citing works
Self-citationGenetics of Aggression in Voles
Gobrogge, K. L., & Wang, Z. (2011) · Advances in genetics · doi:10.1016/b978-0-12-380858-5.00003-4 · Cited by 26 · see citing works
Taesotikul, S., Dilokpattanamongkol, P., Tangsujaritvijit, V., & Suthisisang, C. C. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.1928616 · Cited by 23 · see citing works
Kabelik, D., Alix, V. C., Singh, L. J., Johnson, A. L., Choudhury, S. C., Elbaum, C. C., & Scott, M. R. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.026 · Cited by 22 · see citing works
Morphine withdrawal-facilitated aggression is attenuated by morphine-conditioned stimuli
Sukhotina, I. A. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00429-9 · Cited by 22 · see citing works
Chronic passive exposure to aggression decreases D2 and 5-HT1B receptor densities
Suzuki, H., Han, S. D., & Lucas, L. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.01.018 · Cited by 21 · see citing works
Felip, C. M., Rodríguez‐Arias, M., Fernández‐Espejo, E., Miñarro, J., & Stinus, L. (2000) · Behavioral Neuroscience · doi:10.1037//0735-7044.114.2.424 · Cited by 19 · see citing works
Kudryavtseva, N. N. (2020) · Aggression and Violent Behavior · doi:10.1016/j.avb.2020.101403 · Cited by 18 · see citing works
Interaction of Morphine and Haloperidol on Agonistic and Motor Behaviors of Male Mice
Rodríguez‐Arias, M., Miñarro, J., & Simón, V. M. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00403-0 · Cited by 18 · see citing works
Sex, Drugs, and Violence: Neuromodulation of Attachment and Conflict in Voles
Gobrogge, K. L. (2013) · Current topics in behavioral neurosciences · doi:10.1007/7854_2013_264 · Cited by 16 · see citing works
Interactive role of adenosine and dopamine in the opiate withdrawal syndrome
Stella, L., de Novellis, V., Vitelli, M. R., Capuano, A., Mazzeo, F., Berrino, L., Rossi, F., & Filippelli, A. (2003) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-003-0773-9 · Cited by 16 · see citing works
Zhou, Q., Kindlundh, A. M. S., Hallberg, M., & Nyberg, F. (2004) · Peptides · doi:10.1016/j.peptides.2004.07.011 · Cited by 13 · see citing works
Grimes, J. M., Ricci, L. A., Rasakham, K., & Melloni, R. H. (2005) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195168761.003.0016 · Cited by 9 · see citing works
Straub tail, the deprivation effect and addiction to aggressionPreprint
Kudryavtseva, N. N. (2006) · arXiv (Cornell University) · doi:10.48550/arxiv.q-bio/0602017 · Cited by 8 · see citing works
GHB differentially affects morphine actions on motor activity and social behaviours in male mice
Maldonado, C. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(03)00222-3 · Cited by 6 · see citing works
Rodríguez‐Arias, M., Felip, C. M., Aguilar, M. A., & Miñarro, J. (2002) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00734-1 · Cited by 6 · see citing works
Russell, N. M., Frier, M. D., Bortolato, M., & Mangieri, R. A. (2026) · Psychopharmacology · doi:10.1007/s00213-025-06938-0 · Cited by 3 · see citing works
Effects of prenatal cocaine and genotype on intermale agonistic behavior in Mus musculus
Hahn, M. E., Benno, R. H., Caldwell, H. M., & Schanz, N. (1997) · Aggressive Behavior · doi:10.1002/(sici)1098-2337(1997)23:3 · Cited by 2 · see citing works
Efectos de la morfina y el haloperidol sobre la conducta agonística en ratones macho
Rodríguez‐Arias, M., & López, J. M. (1996) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 2 · see citing works
Neurochemistry of Opiate Dependence
Maldonado, R. J., Stinus, L., & Koob, G. F. (1996) · Neuroscience intelligence unit · doi:10.1007/978-3-662-22218-8_4
Radke, A. K. (2011) · University of Minnesota Digital Conservancy (University of Minnesota)
The Impact of Substance P (SP) N-Terminal Metabolite SP1-7 in Opioid Tolerance and Withdrawal
Zhou, Q. (2001) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Understanding canine aggression: Neurobiological insights for a complex behavior
Güvenç, G., & Semen, Z. (2023) · Journal of Istanbul Veterinary Sciences · doi:10.30704/http-www-jivs-net.1272983
Aggression and repeated alcohol drinking-in-the-dark: dissecting subtypes in outbred mice
Frier, M. D., Biggi, N. P., Babb, J. A., Newman, E. L., Covington, H. E., & Weera, M. M. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07025-8
Pellis, S. M. (1993) · doi:10.1002/1098-2337(1993)19:5
- Authors
- Tidey, J. W., & Miczek, K. A.
- Affiliations
- Tufts University (US)
- Venue
- Psychopharmacology
- Published
- 1992-07
- Volume
- 108
- Issue
- 1-2
- Pages
- 177-184
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2007301748
- Cited by
- 48
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA05122)
- National Institute on Drug Abuse (DA-02632, R01DA002632)
- 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
- morphine withdrawal, aggression, dopamine D1 receptor, dopamine D2 receptor, SKF 38393, quinpirole, dopamine agonists, motor behavior, rearing behavior, walking, resident-intruder aggression, opioid withdrawal
- MeSH terms
- Aggression, Animals, Body Temperature, Dose-Response Relationship, Drug, Drug Implants, Ergolines, Male, Morphine, Motor Activity, Substance Withdrawal Syndrome, Dopamine Agents, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Receptors, Dopamine D1, Receptors, Dopamine D2, Quinpirole, Mice
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