Increased intravenous morphine self-administration following Roux-en-Y gastric bypass in dietary obese rats

• RYGB in high fat dietary rats increased self-administration of morphine.
• The effects were independent of weight loss: did not occur in weight-matched rats.
• The findings are consistent with clinical data and suggest a biological mechanism.

Roux-en-Y gastric bypass (RYGB) surgery is a commonly performed and very effective method to achieve significant, long-term weight loss. Opioid analgesics are primarily used to manage postoperative pain as fewer alternative medication options are available for bariatric surgery patients than for the general population. Recent clinical studies support a greater risk for substance use following bariatric surgery, including an increased use of opioid medications. The present study is the first to study morphine self-administration in a rat model of RYGB. High fat diet-induced obese (HFD-DIO) rats underwent RYGB (n = 14) or sham-surgery with ad libitum HFD (SHAM, n = 14) or a restricted amount that resulted in weight matched to the RYGB cohort (SHAM-WM, n = 8). An additional normal-diet (ND, n = 7), intact (no surgery) group of rats was included. Two months after the surgeries, rats were fitted with jugular catheters and trained on a fixed ratio-2 lick task to obtain morphine intravenously. Both morphine-seeking (number of licks on an empty spout to obtain morphine infusion) and consumption (number of infusion) were significantly greater in RYGB than any control group beginning on day 3 and reached a two-fold increase over a period of two weeks. These findings demonstrate that RYGB increases motivation for taking morphine and that this effect is independent of weight loss. Further research is warranted to reveal the underlying mechanisms and to determine whether increased morphine use represents a risk for opioid addiction following RYGB. Identifying risk factors preoperatively could help with personalized postoperative care to prevent opioid abuse and addiction.