Alterations in morphine-induced reward, locomotor activity, and thermoregulation in CREB-deficient mice
Abstract
Previous studies in our lab have shown a robust decrease in the rewarding properties of morphine in CREB(alphaDelta) mutant mice. To determine whether the genetic effects of the global CREB(alphaDelta) mutation are specific to reward or generalizable, we examined a variety of morphine-induced behaviors regulated by different neural circuitry. At low doses of morphine (5 and 10 mg/kg), CREB(alphaDelta) mutant mice show a reduction in reward yet similar locomotor activity in response to morphine compared to wild type littermates. However, at a high dose (20 mg/kg), CREB(alphaDelta) mutant mice show an increase in reward and locomotor activity. Morphine-induced thermoregulation is attenuated in CREB(alphaDelta) mutant mice at high doses of morphine compared to wild type animals. The behavioral differences in response to morphine seen in CREB(alphaDelta) mutant mice are not due to changes in mu opioid receptor (MOR) mRNA expression, as the CREB deletion has no effect on baseline MOR mRNA in three of the brain regions involved in mediating these behaviors: the ventral tegmental area (VTA), nucleus accumbens (NAc), and hypothalamus. These data demonstrate that at low doses, deficits in morphine-induced changes in CREB deficient mice are limited to reward and thermoregulation. However, at higher doses, CREB mutant mice actually find morphine more rewarding and exhibit increased locomotor activity compared to their wild type littermates. Together, these results indicate that the role of CREB in dose-dependent changes in behaviors induced by morphine is different depending on the brain regions involved in mediating the behavior.
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Increased CREB activity in the NAc is negatively related to behavioral responses to cocaine, opiates, and alcohol in numerous experimental systems.
“in numerous experimental systems, increased CREB activity in the NAc is negatively related to behavioral responses to cocaine, opiates, and alcohol [86,88-90].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [90]
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- Authors
- Walters, C. L., Godfrey, M., Li, X., & Blendy, J. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Blendy, Julie A.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 1032
- Issue
- 1-2
- Pages
- 193-199
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2159529738
- Cited by
- 39
- References
- 40
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2017: 2 · 2016: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f31da015949-01)
- National Institute on Drug Abuse (1F31 DA 015949, R01DA011649, DA116-49-01A2)
- 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
- CREB, morphine, opioid reward, locomotor activity, thermoregulation, mu-opioid receptor, dose-dependent effects, ventral tegmental area, nucleus accumbens, hypothalamus, opioid tolerance
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Body Temperature Regulation, Brain, Conditioning, Operant, Dose-Response Relationship, Drug, Morphine, Motor Activity, Reward, RNA, Messenger, Time Factors, Cyclic AMP Response Element-Binding Protein, Receptors, Opioid, mu, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Mice
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