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Updated: Oct 21, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
High-fat diet attenuates morphine withdrawal effects on sensory-evoked locus coeruleus norepinephrine neural activity
Xinyi Li1, Chung-Yang Yeh2, Nicholas T Bello1
1Department of Animal Sciences, Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Abstract:
Objective: These experiments sought to characterize the effects of obesity propensity and obesogenic diet on locus coeruleus (LC) norepinephrine (NE) activity and determine the effects of obesity on LC neural responses to morphine withdrawal.Methods: In vivo single-unit LC electrophysiological activity was measured in obese prone (OP) and obese resistant (OR) male SD rats following high-fat (HFD: 45% fat) or low-fat (LFD; 10% fat) feeding. A separate cohort of LFD and HFD rats underwent in vivo LC recording on day 3 of spontaneous morphine withdrawal following an escalation dose paradigm (5-15 mg/kg; SQ twice daily).Results: OP (LFD: 34 cells/7 rats; HFD: 32 cells/6 rats) had higher spontaneous and tonic activity, and lower sensory-evoked activity compared with OR (LFD: 31 cells/6 rats; HFD: 41 cells/7 rats). Interacting effect of diet x strain status was observed on signal-to-noise ratio with OR-LFD having higher ratio than OP-LFD and OP-HFD. Morphine treatment decreased body weights. Withdrawal increased sensory-evoked rate in LFD (morphine; 20 cells/10 rats; saline 24 cells/6 rats) but not HFD (saline: 22 cells/7 rats; morphine: 21 cells/5 rats) rats. In a separate group of age-matched SD rats, a similar weight loss (5-7%) in response to the morphine did not alter sensory-evoked rate but decreased signal-to-noise ratio (Control: 22 cells/8 rats; Weight-matched: 23 cells/8 rats).Discussion: Taken together, our findings suggest that obesity and diet alter the sensory-evoked LC-NE neural responses, which could have implication for emotional stress and opioid-withdrawal behaviors.
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