Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain
Abstract
Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinson's disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.
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6-OHDA-treated rats exhibit severe sleep deficits, including significant circadian disruption.
“6-OHDA-treated rats exhibit severe sleep deficits, including significant circadian disruption (Gravotta et al., 2011).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Gravotta et al., 2011
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Genetic interaction between circadian and homeostatic regulation of sleep
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Animal models of central nervous system disorders
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HYPERSOMNIA AND CIRCADIAN DISTURBANCES IN PARKINSON’S DISEASE
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Regulation of Transmission at Monoaminergic Neurons: A Synapse-to-Circuit Study in Drosophila
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(2015) · Neurotransmitter · doi:10.14800/nt.414
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- Authors
- Gravotta, L., Gavrila, A. M., Hood, S., & Amir, S.
- Affiliations
- Concordia University (CA)
- Corresponding author
- Amir, Shimon
- Venue
- Journal of Molecular Neuroscience
- Published
- 2011-04-12
- Volume
- 45
- Issue
- 2
- Pages
- 162-171
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- OpenAlex
- W2157520586
- Cited by
- 74
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 11 · 2016: 8 · 2015: 5 · 2014: 8 · 2013: 4 · 2012: 6
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Neuroscience (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 › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- dopamine depletion, 6-hydroxydopamine, circadian rhythm, wheel running, Period2, suprachiasmatic nucleus, dorsal striatum, bed nucleus of the stria terminalis, limbic forebrain, intracerebroventricular administration, Parkinson's disease, clock genes
- MeSH terms
- Animals, Circadian Rhythm, Dopamine, Limbic System, Male, Motor Activity, Oxidopamine, Rats, Wistar, Adrenergic Agents, Rats, Period Circadian Proteins, Infusions, Intraventricular
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