Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
Open accessAbstract
Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.
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Other biological mechanisms that affect behavior, such as the endogenous opioid system, may have effects that go undetected.
“Other biological mechanisms that affect behavior, such as the endogenous opioid system, may have effects that go undetected [60,61].”
From Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain (2022) · cites this paper as [61]
The Discussion links morphine’s behavioral effects to the opioidergic system and says that basic locomotion alone cannot capture all facets of drug-induced behavioral change. This supports the possibility that a limited behavioral measure could miss effects, but the paper does not specifically address undetected effects of the endogenous opioid system. (LLM, conf=0.78)
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References 47 · Cited by 24
Research works printed but not linked: 1
- [38]Rodriguiz R.M. Wetsel W.C. Frontiers in Neuroscience Assessments of Cognitive Deficits in Mutant Mice Animal Models of Cognitive Impairment Levin E.D. Buccafusco J.J. CRC Press/Taylor & Francis, Taylor & Francis Group, LLC. Boca Raton, FL, USA 2006 21204369
- Authors
- Paul, A. K., Gueven, N., & Dietis, N.
- Affiliations
- University of Tasmania (AU)
- University of Cyprus (CY)
- Corresponding author
- Paul, Alok K.
- Dietis, Nikolas
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2021-07-19
- Volume
- 26
- Issue
- 14
- Pages
- 4355
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8308092
- OpenAlex
- W3186203774
- Cited by
- 24
- References
- 47
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 3
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UTAS Research Repository (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- University of Cyprus
- University of Tasmania
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- morphine, behavioral tolerance, motor behavior, locomotor activity, antinociception, analgesic tolerance, high-dose morphine, open field behavior, tail flick, hot plate, opioid side effects
- MeSH terms
- Analgesics, Opioid, Animals, Behavior, Animal, Dose-Response Relationship, Drug, Male, Morphine, Motor Activity, Pain, Rats, Sprague-Dawley, Rats
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