Nutritional supplementation of nucleotides restores opioid CNS-mediated phenomena in mice

Previous experiments have demonstrated that suppression of immune function by either cyclosporin A or by a nucleotide free (NF) diet results in attenuation of morphine withdrawal symptoms in mice suggesting that immune status impacts CNS opioid-related phenomena. The present study elaborates on these initial findings by examining the effects of repletion of the NF diet with nucleotides or their precursors on opiate withdrawal. Female Balb/c mice were divided into six groups: a control group (C) given a standard lab chow diet and five experimental groups each given one of the following diets: a nucleotide free diet (NF); the NF supplemented with 0.25% RNA (NFR 0.25); the NF supplemented with 2.5% RNA (NFR 2.5) the NF supplemented with 0.06% uracil (NFU 0.06); the NF supplemented with 0.6% uracil (NFU 0.6). The mice were made morphine dependent by subcutaneous implantation of morphine pellets. Seventy-two hours after morphine pellet implantation, withdrawal was precipitated with naloxone (2 mg/kg). The mice were then observed and two indicators of withdrawal scored: jumping and diarrhea. The NF, NFR 0.25, NFR 2.5 and NFU 0.06 groups demonstrated significantly attenuation of the withdrawal signs relative to control animals. The NFU 0.6 group, however, had withdrawal scores restored to near control levels for both jumping and diarrhea. This suggests that nucleotides, particularly uracil, may play an important role in the immune-to-brain signaling pathway.