The Effect of Probiotic Supplementation on Morphine Preference in Rats: Possible Antioxidative/Oxidative Signaling Pathway

Background: Many studies have revealed various aspects of the relationship between the stomach and the brain, but there has been no systematic study of the role of gut microbiota in drug addiction to date. This investigation is based on the novel concept that gut dysbiosis plays an important role in addiction disorders. Probiotic supplements (PBS) are thought to be a useful therapy method for opiate addiction and substance misuse. Therefore, it is postulated that changes in gut flora can play a significant part in the addiction process. Objectives: The aim of this study was to observe whether PBS, through the gut-brain axis in drug addiction, can decrease morphine (Mor) tendency in rats by affecting oxidative stress (OS) markers, using a conditioned place preference (CPP) paradigm. Methods: Forty-two rats (weight 180 - 200 g) were divided into six groups (n = 7 in each). The effective dose of morphine (Mor) was 7.5 mg/kg. Two probiotic supplements were used: Prodigest (Prd) containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum, and Prokid (Prk) containing Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus rhamnosus, and Bifidobacterium bifidum. These were administered via gavage for 14 days. The animals were given PBS after each conditioning session in the conditioned place preference (CPP) model. The animals' locomotor activity was then evaluated using an open field apparatus. The brain was tested for malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and thiol levels. Results: Only the Prd group, but not the Prk group, significantly increased the time spent in the Mor chamber (the location preference index) during the acquisition phase (P < 0.05). The anti-oxidation/oxidation profiles (MDA, NO, CAT, SOD, TAC, and thiol) were altered by PBS. Conclusions: Given the elevated location preference index generated by Mor, it may be argued that PBS influences mood and behavior via antioxidative/oxidative signaling, thereby potentiating the effect of Mor.