NUTRITIONAL SUPPLEMENTATION OF NUCLEOTIDES RESTORES OPIOID CNS-MEDIATED PHENOMENA IN MICE

Previous experiments have demonstrated that suppression of immune func tion by either cyclosporin A or by a nucleotide free (NF) diet results in attenuation of morphine withdrawal symptoms in mice suggesting tha t immune status impacts CNS opioid-related phenomena. The present stud y elaborates on these initial findings by examining the effects of rep letion of the NF diet with nucleotides or their precursors on opiate w ithdrawal. 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); th e 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); t he NF supplemented with 0.6% uracil (NFU 0.6). The mice were made morp hine dependent by subcutaneous implantation of morphine pellets. Seven ty-two hours after morphine pellet implantation, withdrawal was precip itated with naloxone (2 mg/kg). The mice were then observed and two in dicators 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 bot h jumping and diarrhea. This suggests that nucleotides, particularly u racil, may play an important role in the immune-to-brain signaling pat hway.