High-fat diet attenuates morphine withdrawal effects on sensory-evoked locus coeruleus norepinephrine neural activity in male obese rats

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.

KEYWORDS:

• Opioid induced weight change
• locus coeruleus-norepinephrine system
• diet-induced
• hyperarousal
• restriction
• opioid misuse
• pain management
• obesity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are available from the corresponding author upon individual request.

Additional information

Funding

This study was supported by Rutgers Department of Animal Sciences, USDA-NIFA NJ06180, and USDA-NIFA NJ06280. Technical assistance was also provided by Dr. Jessica L. Verpeut for the HPLC analysis.

Notes on contributors

Xinyi Li

Xinyi Li is a Ph.D. candidate in the School of Biological and Environment Sciences at Rutgers University. Her work focuses on neurobiological overlaps between obesity and opioid misuse.

Chung-Yang Yeh

Chung-Yang Yeh, Ph. D. is a postdoctoral researcher in the Department of Medicine, University of Wisconsin-Madison. His work focuses on the interaction of dietary protein contents and longevity.

Nicholas T. Bello

Nicholas T. Bello, Ph.D. is an Associate Professor in the Department of Animal Sciences at Rutgers University. His work focuses on attentional and arousal processes of binge-like eating and obesity. Additional projects examine the effectiveness and safety of dietary supplements for weight loss.