Roux-en-Y gastric bypass increases GABA-A receptor levels in regions of the rat brain involved in object recognition memory and perceptual acuity

Roux-en-Y gastric bypass surgery (RYGB), one of the most common and successful procedures for combatting obesity, is associated with post-surgery substance use disorder (SUD) and other addictive behaviors in a subset of patients. We investigated the effects of RYGB on GABA-A receptor levels in the rat brain to identify potential mechanisms of this behavior. The GABAergic system is affected in addiction and has been implicated in the pathology of obesity. We assigned male Sprague-Dawley rats to four groups: standard, low fat diet with sham surgery (control), ad libitum HFD with sham surgery (Sham), calorie restricted HFD with sham surgery (Sham-FR), or HFD with RYGB surgery. Surgery was performed after 8 weeks on the control or HFD diet. Rats maintained their respective diets for 9 weeks post-surgery, then were sacrificed for GABA-A receptor autoradiography using the [³H] Flunitrazepam ligand. We identified increased GABA-A binding in the perirhinal cortex of ad-libitum HFD fed rats compared to normal diet controls. RYGB surgery increased GABA-A in the ectorhinal cortex compared to normal diet controls, and increased binding in the jaw region of the primary somatosensory cortex compared to food-restricted rats that received sham surgery. Hypothalamus GABA-A was also negatively correlated with body weight in the RYGB group, where GABA signaling may play a role in obesity regulation. These results suggest that HFD and RYGB modulate GABA signaling in regions important for object recognition memory, and that increased GABA-A levels in the jaw's perceptual field cortex arise from the surgery itself, independent of caloric restriction.