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Neurochemical and behavioral effects of corticotropin-releasing factor in the ventral tegmental area of the rat
Abstract
Corticotropin-releasing factor (CRF) is thought to have a neurotransmitter function in the mammalian central nervous system. The release of CRF into the hypothalamic-hypophyseal portal system in response to stress is known, and it has been suggested that CRF may function elsewhere in the central nervous system to promote stress-induced physiological and behavioral changes. Acute stress has been shown to activate dopamine (DA) neurons in the ventral tegmental area (VTA) that project to the prefrontal cortex. To determine whether CRF may act in the VTA to activate the mesocortical or mesolimbic DA systems, it was injected into the VTA of rats, and changes in spontaneous motor behavior and DA metabolism were measured. Intra-VTA injection of CRF produced a dose-dependent increase in horizontal and vertical photocell counts with a minimal effective dose of 0.01 and 0.1 nmol, respectively. In contrast, the minimal effective dose for CRF-stimulated motor behavior after injection into the lateral ventricles was 0.3 nmol for horizontal activity. Furthermore, in the open field, the behavioral profile of CRF (0.3 nmol) given intra-VTA differed from that observed after intraventricular injection. The motor stimulant effect of intra-VTA CRF was not blocked by pretreatment with the DA receptor antagonist haloperidol. After intra-VTA injection, CRF produced a dose-dependent decrease in DA metabolism in the prefrontal cortex. The decrease in DA metabolism in the prefrontal cortex was present at 30 and 60 min but not at 120 min after injection, and in the nucleus accumbens DA metabolism was increased only at 60 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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“Postnatally, CRF and glucocorticoids can potentiate dopamine release (Bagosi et al., 2006; Kalivas et al., 1987; Piazza et al., 1996).”
From The effects of early life stress on reward processing (2018) · cites this paper as Kalivas et al., 1987
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Items 101–136 of 136
Ryabinin, A. E., Cocking, D. L., & Kaur, S. (2013) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2013.05.004 · Cited by 20
“Multiple examples showing influences of the CRF/Ucn system on reward pathways have been reported (Kalivas et al., 1987; * Corresponding author.”
Effects of medial prefrontal cortex and dorsal striatum lesions on retrieval processes in rats
Botreau, F., Massioui, N. E., Chéruel, F., & Gisquet-Verrier, P. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.032 · Cited by 20
Chang, S., Fermani, F., Lao, C. L., Huang, L., Jakovcevski, M., Giaimo, R. D., Gagliardi, M., Menegaz, D., Hennrich, A. A., Ziller, M. J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo1023 · Cited by 19
“Notably, the minimal effective CRH dose to reach similar effects via injection in the lateral ventricle was 30 times higher compared to the intra-VTA injection ( 42 ).”
The effects of acute stress on Pavlovian-instrumental transfer in rats
Pielock, S. M., Braun, S., & Hauber, W. (2012) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-012-0129-3 · Cited by 18
Gurkovskaya, O. V., Palamarchouk, V. S., Smagin, G. N., & Goeders, N. E. (2005) · Synapse · doi:10.1002/syn.20172 · Cited by 17
“Supporting this notion, CRH administered directly into the VTA did not change the overall content of dopamine or its metabolites in the NAC, but diminished the ratio of dopamine metabolites to dopamine (i.e., turnover) in the prefrontal cortex (Kalivas et al., 1987).”
BackgroundResultInfluentialConti, L. H. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.11.055 · Cited by 17
Corticotropin-releasing factor activates tyrosine hydroxylase in rat and mouse striatal homogenates
Olianas, M. C., & Onali, P. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90025-8 · Cited by 16
Bagosi, Z., Jászberényi, M., Bujdosó, E., & Telegdy, G. (2006) · Neurochemical Research · doi:10.1007/s11064-005-9010-x · Cited by 15
“The injection of CRF in the ventral tegmental area (VTA) produced a dose-dependent increase in motor activity in rats, and an increase in the DA metabolism in the nucleus accumbens [12].”
BackgroundStress, the Hypothalamic—Pituitary—Adrenal Axis, and Depression
Ritchie, J., & Nemeroff, C. B. (1991) · Elsevier eBooks · doi:10.1016/b978-0-12-482490-4.50013-4 · Cited by 14
Nasihatkon, Z. S., Khosravi, M., Bourbour, Z., Sahraei, H., Ranjbaran, M., Hassantash, S. M., Sahraei, M., & Baghlani, K. Z. (2014) · Behavioural Neurology · doi:10.1155/2014/294149 · Cited by 15
“to the VTA and it seems that these inputs along with the dopaminergic projections from ventral tegmental to nucleus accumbens, amygdala, and prefrontal cortex modulate the activity of stress system in the animals [6, 7, 9, 10, 14–21].”
Lawrence, A. J., Parish, C. L., Chen, F., Lodge, D. J., Krstew, E., Card, K., Finkelstein, D. I., & Horne, M. K. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03300.x · Cited by 13
“Intra-VTA injections of CRF increase spontaneous motor activity, but this cannot be blocked with haloperidol (Kalivas et al. 1987) although CRF requires an intact dopaminergic system to enhance enkephalin and dynorphin release within striatal slices (Sirinathsinghji et al. 1990), whereas j-opioid…”
Corticotropin-Releasing Factor, Stress, and Animal Behavior
Cole, B. J., & Koob, G. F. (1991) · Elsevier eBooks · doi:10.1016/b978-0-12-482490-4.50011-0 · Cited by 13
Bueno-Nava, A., González-Piña, R., Alfaro-Rodríguez, A., Ávila-Luna, A., Arch-Tirado, E., & Alonso-Spilsbury, M. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0790-5 · Cited by 12
Smagin, G. N., & Goeders, N. E. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.02.004 · Cited by 12
“Accordingly, the administration of CRH directly into the VTA results in a time-dependent decrease in prefrontal cortical dopamine metabolism with an increase in dopamine turnover in the nucleus accumbens (Kalivas et al., 1987).”
BackgroundBehavioral and neuroendocrine actions of the Met-enkephalin-related peptide MERF
Bujdosó, E., Jászberényi, M., Farkas, J., Tóth, G., Wollemann, M., & Telegdy, G. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(03)00004-7 · Cited by 9
CONTI, L., Berridge, C. W., & Tayler, J. E. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.08.009 · Cited by 9
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Cancela, L. M., Mongi‐Bragato, B., Avalos, M. P., & Bollati, F. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010385 · Cited by 9
“However, studies directly assessing the role of VTA CRF in regulating mesocortical DA output have yielded mixed results [102].”
Pohorecky, L. A., Sweeny, A., & Buckendahl, P. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2339-8 · Cited by 6
“2010) contributed to the differences in DArgic function associated with social stress, which may underlie the greater sensitivity to AMP of the DOM rats; extra-hypothalamic effects of corticotropin releasing factor include activation of DArgic system and of locomotor and rearing behaviors (Kalivas et al. 1987; Wanat e…”
A final common pathway for depression: implications for therapy
Stone, E. A. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.8.1019 · Cited by 6
“CRF is also known to stimulate motor behavior from the ventral tegmental area [115] .”
BackgroundBurns, L. H., & Kelley, A. E. (1988) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(88)90343-7 · Cited by 6
Animal models for studying therapeutic targets and treatments for alcohol use disorder
Favoretto, C. A., Righi, T., Fernandes, G. J. D., Bertagna, N. B., Rodolpho, B. T., Janisset, N. R. L. L., Jovita-Farias, C., Costa, G. V. L., Anjos-Santos, A., da Silva, F. B. R., et al. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.08.004 · Cited by 4
Lalonde, R., & Strazielle, C. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0075 · Cited by 4
“In contrast, CRH injected in the ventral tegmental area increased horizontal and vertical photocell counts in a novel open-field (Kalivas et al., 1987), although it usually does so in a familiar one.”
BackgroundGenetics of Endocrine-Behavior Interactions
Müller, M. B., Keck, M. E., Steckler, T., & Holsboer, F. (2002) · Elsevier eBooks · doi:10.1016/b978-012532104-4/50093-7 · Cited by 4
Douma, T. N., Millan, M. J., Boulay, D., Griebel, G., Verdouw, P. M., Westphal, K. G. C., Olivier, B., & Groenink, L. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3315-2 · Cited by 3
“Third, CRF has been reported to increase dopaminergic activity in the ventral tegmental area (Wanat et al. 2008), NAc (Kalivas et al. 1987; Pan et al. 1995), and PFC (Dunn and Berridge 1987; Lavicky and Dunn 1993), although decreases have also been reported in the PFC (Kalivas et al. 1987; Izzo et…”
BackgroundNeurobiology of Stress and Risk for Relapse
Erb, S. M. (2007) · Elsevier eBooks · doi:10.1016/b978-012370632-4/50010-3 · Cited by 3
Onali, P., & Olianas, M. C. (1990) · Brain Research · doi:10.1016/0006-8993(90)91219-7 · Cited by 3
Kelly, E. A., Love, T., & Fudge, J. L. (2023) · Synapse · doi:10.1002/syn.22284 · Cited by 2
“…is found in some of these afferent sources, and is a neuromodulator of DA cell firing, although the precise mechanism is not understood (Gallagher et al., 2008; Grieder et al., 2014; Kalivas et al., 1987; Orozco-Cabal et al., 2006; Ungless et al., 2003; Wanat et al., 2008; Wanat et al., 2013).”
BackgroundWilliams, R. G., Li, K., & Phillips, P. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.814218 · Cited by 2
Four hypothalamic peptides and their impact on drug-seeking behaviour: A prefrontal cortex view
Perry, C. J., & Cornish, J. L. (2022) · Addiction Neuroscience · doi:10.1016/j.addicn.2022.100018 · Cited by 1
Gallardo, N., & Andrea, V. (2014)
Olianas, M. C., & Onali, P. (1988) · Pharmacological Research Communications · doi:10.1016/s0031-6989(88)80744-6
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Borges, A. C. (2015) · RIUnB Institutional Repository (University of Brasília) · doi:10.26512/2015.06.t.18631
The Impact of Repeated Stress on Neuropeptidergic Regulation of Monoamine Systems
Lemos, J. C. (2012) · ResearchWorks at the University of Washington (University of Washington)
Grieder, T. E. (2012) · TSpace (University of Toronto)
Metadata
- Authors
- Kalivas, P. W., Duffy, P., & Latimer, L. G.
- Affiliations
- Washington State University (US)
- ORCID
- Kalivas, P W
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1987-09
- Volume
- 242
- Issue
- 3
- Pages
- 757-763
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2272340543
- Cited by
- 137
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 6
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institute of Mental Health (MH-40817)
- National Institute on Drug Abuse (DA03906)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- corticotropin-releasing factor, ventral tegmental area, dopamine metabolism, mesolimbic dopamine system, mesocortical dopamine system, motor stimulation, prefrontal cortex, nucleus accumbens, stress, haloperidol, intraventricular injection
- MeSH terms
- Animals, Corticotropin-Releasing Hormone, Dopamine, Dose-Response Relationship, Drug, Frontal Lobe, Haloperidol, Male, Motor Activity, Naloxone, Rats, Inbred Strains, Tegmentum Mesencephali, Rats
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