Circadian Rhythms of Dopamine and Cholecystokinin in Nucleus Accumbens and Striatum of Rats—Influence on Dopaminergic Stimulation
Abstract
The concentrations of cholecystokinin (CCK) and dopamine (DA) were determined in the nucleus accumbens (anterior, posterior) and striatum of rats every 2 h during a period of 24 h. For both substances, a circadian rhythm was found, which was best fitted by a dominant 24-h period superimposed by the second (12 h) and fourth (6 h) harmonics. The rhythms in CCK and DA were negatively correlated because of a difference in phase position by approximately 3 h. A dominant DA peak was found in the light phase coinciding with a trough in CCK and vice versa in the dark phase. Based on these data, CCK and DA were determined in rats treated with gamma-butyrolactone (GBL; inhibitor of DA release) or thyrotropin-releasing hormone (TRH; stimulator of DA release) at 0900 h or 1300 h to study a putative time-dependency in drug effects. After GBL treatment, CCK as well as DA increased by up to 200% whereas TRH administration led to a rather complex alteration, inasmuch as CCK was increased or decreased, depending on circadian time, whereas the rhythmic pattern in DA remained relatively unaffected. Comparing the drug effects obtained at 0900 h with the response seen at 1300 h revealed significant quantitative as well as qualitative differences. The results demonstrate that the neurotransmission system investigated changed its level of activity depending on time of day. No changes were obtained that convincingly may be ascribed to colocalization of DA and CCK. It is concluded that the chronobiological data indicate a close interaction of CCK and DA in various areas of the rat brain, independent of colocalization.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Neural systems associated with affect, such as limbic brain regions, monoamine neurotransmitters, and the hypothalamic-pituitary-adrenal axis, are all under circadian regulation.
“Notably, neural systems associated with affect, such as the limbic brain regions, monoamine neurotransmitters, and the hypothalamic–pituitary–adrenal axis (HPA), are all under circadian regulation27–31.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [29]
Cites
New peptide in the vertebrate CNS reacting with antigastrin antibodies
Vanderhaeghen, J. J., SIGNEAU, J. C., & Gepts, W. (1975) · Nature · doi:10.1038/257604a0 · Cited by 757 · see citing works
Evidence for coexistence of dopamine and CCK in meso-limbic neurones
Hökfelt, T. G. M., Rehfeld, J. F., Skirboll, L. R., IVEMARK, B. I., Goldstein, M., & MARKEY, K. (1980) · Nature · doi:10.1038/285476a0 · Cited by 707 · see citing works
Johansson, O., Hökfelt, T. G. M., Pernow, B., Jeffcoate, S. L., White, N., Steinbusch, H. W. M., Verhofstad, A. A. J., Emson, P. C., & Spindel, E. R. (1981) · Neuroscience · doi:10.1016/0306-4522(81)90028-2 · Cited by 700 · see citing works
Kuczenski, R. T., & Segal, D. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-06-02051.1989 · Cited by 398 · see citing works
Distribution of gastrin and CCK-like peptides in rat brain
Lor�n, I., Alumets, J., H�kanson, R., & Sundler, F. (1979) · Histochemistry and Cell Biology · doi:10.1007/bf00689607 · Cited by 277 · see citing works
Daily fluctuation (circadian and ultradian) in biogenic amines of the rat brain
Scheving, L. E., Harrison, W., Gordon, P., & Pauly, J. E. (1968) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1968.214.1.166 · Cited by 204 · see citing works
Chronopharmacology: Cellular and biochemical interactions
(1990) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(90)90467-z · Cited by 137 · see citing works
Chan‐Palay, V. (1979) · Anatomy and Embryology · doi:10.1007/bf00299625 · Cited by 103 · see citing works
PHARMFIT—a Nonlinear Fitting Program for Pharmacology
Mattes, A., Witte, K. K., Hohmann, W., & Lemmer, B. (1991) · Chronobiology International · doi:10.3109/07420529109059182 · Cited by 102 · see citing works
Self-citationDiurnal rhythm in the central dopamine turnover in the rat
Lemmer, B., & Berger, T. (1978) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00498052 · Cited by 75 · see citing works
Self-citationCrawley, J. N. (1989) · Synapse · doi:10.1002/syn.890030408 · Cited by 40 · see citing works
O‘Neill, M. F., Dourish, C. T., & Iversen, S. D. (1991) · European Journal of Pharmacology · doi:10.1016/0014-2999(91)90037-q · Cited by 37 · see citing works
24-hour variation in content and release of hypothalamic neuropeptides in the rat
Nicholson, S. A., Adrian, T. E., Bacarese-Hamilton, A. J., Gillham, B., Jones, M. T., & Bloom, S. R. (1983) · Regulatory Peptides · doi:10.1016/0167-0115(83)90110-6 · Cited by 36 · see citing works
Demarest, K. T., Lawson-Wendling, K. L., & Moore, K. E. (1983) · Biochemical Pharmacology · doi:10.1016/0006-2952(83)90494-x · Cited by 31 · see citing works
Bhaskaran, D., & Radha, E. (1984) · Experimental Gerontology · doi:10.1016/0531-5565(84)90034-2 · Cited by 30 · see citing works
Modulation of cholecystokinin release from posterior nucleus accumbens by D-2 dopamine receptor
Martin, J. R., Beinfeld, M. C., & Wang, R. Y. (1986) · Brain Research · doi:10.1016/0006-8993(86)90626-8 · Cited by 25 · see citing works
Cholecystokinin--gene structure, and molecular forms in tissue and blood.
Eysselein, V. E., Reeve, J. R., & Eberlein, G. A. (1986) · PubMed · Cited by 23 · see citing works
Chapter 25 Neurotransmitter colocalization and circadian rhythms
Albers, H. E., Liou, S., Stopa, E. G., & Zoeller, R. T. (1992) · Progress in brain research · doi:10.1016/s0079-6123(08)61184-x · Cited by 23 · see citing works
Hutchison, J. B., Strupish, J. W., & Nahorski, S. R. (1986) · Brain Research · doi:10.1016/0006-8993(86)90485-3 · Cited by 21 · see citing works
Opacka‐Juffry, J., Tacconelli, F., & Coen, C. W. (1988) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)80583-6 · Cited by 21 · see citing works
Murrin, L. C., & Roth, R. H. (1976) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00509766 · Cited by 19 · see citing works
Dopaminergic agents affected neuronal transmission of cholecystokinin in the rat brain
Fukamauchi, F., Yoshikawa, T., Kaneno, S., Shibuya, H., & Takahashi, R. (1987) · Neuropeptides · doi:10.1016/0143-4179(87)90070-9 · Cited by 18 · see citing works
Systemic administration of thyrotropin-releasing hormone enhances striatal dopamine release in vivo
Kreutz, M. R., Acworth, I. N., Lehnert, H., & Wurtman, R. J. (1990) · Brain Research · doi:10.1016/0006-8993(90)90049-h · Cited by 16 · see citing works
Meyer, D., Holland, A., & Conzelmann, U. (1984) · Neurochemistry International · doi:10.1016/0197-0186(84)90004-4 · Cited by 9 · see citing works
Yoshikawa, T., Fukamauchi, F., Shibuya, H., & Takahashi, R. (1989) · Neurochemistry International · doi:10.1016/0197-0186(89)90037-5 · Cited by 5 · see citing works
Yoshikawa, T., Fukamauchi, F., Shibuya, H., & Takahashi, R. (1989) · Neuropeptides · doi:10.1016/0143-4179(89)90006-1 · Cited by 3 · see citing works
Blood, transmitters and neuropeptides
Schade, R., Vick, K., Sohr, R., Pfister, C., Lemmer, B., & Bellach, J. (1993) · Journal of Interdisiplinary Cycle Research · doi:10.1080/09291019309360223 · Cited by 2 · see citing works
Self-citationEffects of diurnal phase and pimozide on cholecystokinin-elicited hypoactivity in the Hamster
Schnur, P., Espinoza, M., & Flores, R. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90470-z · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
Castañeda, T. R., de Prado, B. M., Prieto, D., & Mora, F. (2004) · Journal of Pineal Research · doi:10.1046/j.1600-079x.2003.00114.x · Cited by 276 · see citing works
Insight into the pathophysiology of restless legs syndrome
Earley, C. J., Allen, R. P., Beard, J. L., & Connor, J. R. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20001201)62:5 · Cited by 216 · see citing works
Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management
Guo, S., Huang, J., Jiang, H., Han, C., Li, J., Xu, X., Zhang, G., Lin, Z., Xiong, N., & Wang, T. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00171 · Cited by 181 · see citing works
Sleipness, E. P., Sorg, B. A., & Jansen, H. T. (2007) · Brain Research · doi:10.1016/j.brainres.2006.10.063 · Cited by 160 · see citing works
Circadian rhythms and addiction: Mechanistic insights and future directions.
Logan, R. W., Williams, W. P., & McClung, C. A. (2014) · Behavioral Neuroscience · doi:10.1037/a0036268 · Cited by 142 · see citing works
A role for the circadian genes in drug addiction
Falcón, E., & McClung, C. A. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.054 · Cited by 135 · see citing works
Circadian clock genes: Effects on dopamine, reward and addiction
Parekh, P. K., Ozburn, A. R., & McClung, C. A. (2015) · Alcohol · doi:10.1016/j.alcohol.2014.09.034 · Cited by 132 · see citing works
Mortality risk factors in sleep apnoea: a matched case–control study
Lavie, P., Herer, P., & Lavie, L. (2007) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2007.00578.x · Cited by 109 · see citing works
Circadian changes in CSF dopaminergic measures in restless legs syndrome
Earley, C. J., Hyland, Κ., & Allen, R. P. (2006) · Sleep Medicine · doi:10.1016/j.sleep.2005.09.006 · Cited by 101 · see citing works
Circadian Rhythms, the Mesolimbic Dopaminergic Circuit, and Drug Addiction
McClung, C. A. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.213 · Cited by 99 · see citing works
Barrière, G., Cazalets, J., Bioulac, B. H., Tison, F., & Ghorayeb, I. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.10.007 · Cited by 99 · see citing works
Circadian patterns of neurotransmitter related gene expression in motor regions of the rat brain
Weber, M., Lauterburg, T., Tobler, I., & Burgunder, J. ‐. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.12.053 · Cited by 94 · see citing works
Luo, A. H., Georges, F. E., & Aston‐Jones, G. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05985.x · Cited by 90 · see citing works
The role of the circadian clock in animal models of mood disorders.
Landgraf, D., McCarthy, M. J., & Welsh, D. K. (2014) · Behavioral Neuroscience · doi:10.1037/a0036029 · Cited by 77 · see citing works
Baird, T. J., & Gauvin, D. V. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00207-5 · Cited by 67 · see citing works
French, I. T., & Muthusamy, K. A. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00114 · Cited by 64 · see citing works
Arey, R. N., Enwright, J. F., Spencer, S. M., Falcon, E., Ozburn, A. R., Ghose, S., Tamminga, C., & McClung, C. A. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.12 · Cited by 62 · see citing works
Becker‐Krail, D. D., Walker, W. H., & Nelson, R. J. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.886704 · Cited by 45 · see citing works
Circadian effects of dopaminergic treatment in restless legs syndrome
Garcı́a-Borreguero, D., Serrano, C., Larrosa, O., & Granizo, J. J. (2004) · Sleep Medicine · doi:10.1016/j.sleep.2004.01.007 · Cited by 37 · see citing works
Csoma, B., & Bikov, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814145 · Cited by 33 · see citing works
Duffy, J. F., Lowe, A., Silva, E. J., & Winkelman, J. W. (2010) · Sleep Medicine · doi:10.1016/j.sleep.2010.06.007 · Cited by 31 · see citing works
Insights into the Role of the Habenular Circadian Clock in Addiction
Salaberry, N. L., & Mendoza, J. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00179 · Cited by 28 · see citing works
Sleipness, E. P., Jansen, H. T., Schenk, J. O., & Sorg, B. A. (2008) · Synapse · doi:10.1002/syn.20552 · Cited by 28 · see citing works
Photoperiodic suppression of drug reinstatement
Sorg, B. A., Stark, G., Sergeeva, A., & Jansen, H. T. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2010.12.022 · Cited by 25 · see citing works
Epigenetic Regulation of Circadian Clocks and Its Involvement in Drug Addiction
Saad, L., Zwiller, J., Kalsbeek, A., & Anglard, P. (2021) · Genes · doi:10.3390/genes12081263 · Cited by 22 · see citing works
Trotti, L. M., & Rye, D. B. (2011) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52014-2.00047-1 · Cited by 21 · see citing works
Circadian aspects in the pathophysiology of the restless legs syndrome
Garcı́a-Borreguero, D., Larrosa, O., & de la Llave, Y. (2002) · Sleep Medicine · doi:10.1016/s1389-9457(02)00143-0 · Cited by 21 · see citing works
Photoperiod Impacts Nucleus Accumbens Dopamine Dynamics
Jameson, A. N., Siemann, J. K., Melchior, J. R., Calipari, E. S., McMahon, D. G., & Grueter, B. A. (2023) · eNeuro · doi:10.1523/eneuro.0361-22.2023 · Cited by 19 · see citing works
Timing of Morphine Administration Differentially Alters Paraventricular Thalamic Neuron Activity
McDevitt, D. S., & Graziane, N. (2019) · eNeuro · doi:10.1523/eneuro.0377-19.2019 · Cited by 20 · see citing works
Siemann, J. K., Grueter, B. A., & McMahon, D. G. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.12.010 · Cited by 16 · see citing works
The Effect of Amphetamine on Locomotion Depends on the Motor Device Utilized
Della‐Maggiore, V., & Ralph, M. R. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00260-9 · Cited by 15 · see citing works
Pleasure: The missing link in the regulation of sleep
Rial, R. V., Cañellas, F., Gamundı́, A., Akaârir, M., & Nicolau, M. C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.03.012 · Cited by 12 · see citing works
CCK-8 and PGE1: central effects on circadian body temperature and activity rhythms in rats
Szelényi, Z., Hummel, Z., Székely, M., & Pétervári, E. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.025 · Cited by 12 · see citing works
Cincotta, A. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713255 · Cited by 11 · see citing works
Oscillation development for neurotransmitter-related genes in the mouse striatum
Cai, Y., Ding, H., Li, N., Chai, Y., Zhang, Y., & Chan, P. (2010) · Neuroreport · doi:10.1097/wnr.0b013e32832ff30e · Cited by 8 · see citing works
Day-Night Variations in the Concentration of Neurotransmitters in the Rat Lumbar Spinal Cord
Jiménez-Zárate, B. S., Piña-Leyva, C., Rodríguez-Sánchez, M., Florán, B., Jiménez-Zamudio, L. A., & Jiménez‐Estrada, I. (2021) · Journal of Circadian Rhythms · doi:10.5334/jcr.215 · Cited by 8 · see citing works
Restless legs syndrome: pathophysiology and clinical aspects
(2003) · Schweizer Archiv für Neurologie und Psychiatrie · doi:10.4414/sanp.2003.01413 · Cited by 8 · see citing works
Mehranfard, N., Ghasemi, M., & Saboory, E. (2025) · Journal of Neuroendocrinology · doi:10.1111/jne.70065 · Cited by 7 · see citing works
Myopia, Light and Circadian Rhythms
John, R., Backhouse, S., & Andrew, V. (2012) · InTech eBooks · doi:10.5772/29251 · Cited by 6 · see citing works
D3 Receptors and Restless Legs Syndrome
Clemens, S. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_351 · Cited by 5 · see citing works
Circadian Rhythms and Addiction
Barko, K., Shelton, M. A., Seggio, J. A., & Logan, R. W. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812202-0.00013-0 · Cited by 5 · see citing works
Nobrega, A. K. D., & Lyons, L. C. (2017) · Neural Plasticity · doi:10.1155/2017/4723836 · Cited by 4 · see citing works
Cocaine Alters the Daily Activity Patterns of Adult SD Female Rats
Lee, M. J., & Dafny, N. (2014) · Journal of Behavioral and Brain Science · doi:10.4236/jbbs.2014.411051 · Cited by 3 · see citing works
Jeczmien‐Lazur, J. S., Sanetra, A. M., Pradel, K., Izowit, G., Chrobok, Ł., Palus‐Chramiec, K., Piggins, H. D., & Lewandowski, M. H. (2023) · The Journal of Physiology · doi:10.1113/jp283757 · Cited by 2 · see citing works
Astrocytes in the Circadian System: A Promising Target for Mood Disorder Interventions
Liu, P., Li, H., Zhu, Y., Song, S., Kang, L., & Hu, Y. (2026) · Journal of Integrative Neuroscience · doi:10.31083/jin48501 · Cited by 1 · see citing works
Wu, B., Castagnola, E., Robbins, E. M., Kaminsky, M., Sanker, S., McClung, C. A., & Cui, X. T. (2026) · npj Biosensing · doi:10.1038/s44328-026-00095-w · Cited by 1 · see citing works
Dynamics of mother–pup interactions: Tradeoff between environment and physiology.
de Vasconcelos, R. G., Klein, M., Cruz, A. M., & Felício, L. F. (2012) · Psychology & Neuroscience · doi:10.3922/j.psns.2012.2.12 · Cited by 1 · see citing works
Circadian Rhythm of Restless Legs Syndrome
Garcı́a-Borreguero, D., & Hening, W. A. (2009) · Elsevier eBooks · doi:10.1016/b978-075067518-5.10013-8 · Cited by 1 · see citing works
Wu, B., Castagnola, E., Robbins, E. M., Kaminsky, M., Sanker, S., McClung, C. A., & Cui, X. T. (2025) · Research Square · doi:10.21203/rs.3.rs-7403119/v1 · Cited by 1 · see citing works
Transmitter-Interaktion (CCK-Dopamin). Neue Aspekte durch den Einsatz aviärer vitelliner Antikörper
Schade, R., Marburger, A., Morgenstern, R., Henklein, P., & Hlinak, A. (2000) · Ersatz- und Ergänzungsmethoden zu Tierversuchen · doi:10.1007/978-3-7091-6760-1_32
Self-citation
- Authors
- Schade, R., Vick, K., Ott, T., Sohr, R., Pfister, C., Bellach, J., Golor, G., & Lemmer, B.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Anatomische Anstalt (DE)
- Freie Universität Berlin (DE)
- Goethe University Frankfurt (DE)
- Venue
- Chronobiology International
- Publisher
- Informa UK Limited
- Published
- 1995-01
- Volume
- 12
- Issue
- 2
- Pages
- 87-99
- ISSN
- 0742-0528 (ISSN-L)
- 1525-6073
- OpenAlex
- W2086628930
- Cited by
- 56
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chronobiology International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- circadian rhythm, dopamine, cholecystokinin, nucleus accumbens, striatum, gamma-butyrolactone, thyrotropin-releasing hormone, time-dependent drug effects, colocalization, neurotransmitter interactions, light-dark cycle
- MeSH terms
- Animals, Cholecystokinin, Circadian Rhythm, Corpus Striatum, Darkness, Dopamine, Light, Male, Nucleus Accumbens, Organ Specificity, Thyrotropin-Releasing Hormone, Time Factors, 4-Butyrolactone, Rats, Wistar, GABA Modulators, 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
