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

Abstract

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.

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

“…For instance, in human fMRI studies both RYGB and MOR antagonist treatments decrease striatal blood oxygenation level dependent signal when subjects are presented images of HF foods (Cambridge et al, 2013; Scholtz et al, 2014) and in rat macronutrient studies, both RYGB and MOR antagonist treatments suppress fat intake when carbohydrate, fat and protein diets are presented simultaneously (Marks-Kaufman and Kanarek, 1990; Wilson-Pérez et al, 2013). In addition, patients who take opioids before RYGB tend to use higher amounts after surgery (Raebel et al, 2013) and a recent investigation revealed that male RYGB rats have markedly higher morphine self-administration rates on a fixed ratio schedule of reinforcement compared to obese, chronically caloric-restricted and lean counterparts (Biegler et al, 2016). These latter findings strongly support those of the present study of reduced brain MOR signaling after RYGB, which may predispose to a compensatory increase in opioid intake as is typically observed with brain receptor downregulation/desensitization during drug tolerance.…”

RYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats

“…Neither our data nor the studies described above, however, indicate whether the RYGB specifically increased hunger or more generally increased reward function. For example, RYGB rats also increase intravenous self-administration of ethanol (Polston et al, 2013) and morphine (Biegler et al, 2015), and RYGB increases alcohol-use disorders in some patients (Steffen et al, 2015). Delineating the specific functional processes through which RYGB affects motivation is an important issue for future research.…”

Use of prescribed opioids before and after bariatric surgery: prospective evidence from a U.S. multicenter cohort study

“…Second, administering systemic opioid therapy for short-term postoperative pain may increase risk for chronic opioid use(6;18;19). Third, RYGB accelerates the rate of morphine solution absorption(20), and, in animal models, has been shown to increase motivation for taking morphine(21). Collectively, these data suggest that the risk for opioid use and dependence may increase following at least some bariatric surgical procedures.…”