Alteration in the brain content of substance P (1-7) during withdrawal in morphine-dependent rats

Previous studies have shown that substance P (SP) may modulate the abstinen ce reaction to opioid withdrawal. Its N-terminal fragment SP1-7 may inhibit the intensity of the withdrawal reactions in morphine dependent mice, This study was designed to determine whether the endogenous concentrations of t he SP1-7 fragment in the brain are affected during naloxone-precipitated wi thdrawal in the male rat. The amounts of the peptide was assessed by a spec ific radioimmunoassay in extracts of discrete brain regions (including the cerebral cortex, hippocampus. hypothalamus, nucleus accumbens, striatum, su bstantia nigral ventral tegmental area and the spinal cord) during morphine tolerance and withdrawal. The results indicated that the concentrations of SP1-7 were significantly elevated in the ventral tegmental area both in mo rphine tolerant rats anti during naloxone-precipitated withdrawal. During m orphine withdrawal significant increases in the peptide concentration were also observed in the hypothalamus and the spinal cord. It was concluded tha t the enhanced content of SP1-7 may also indicate the involvement of the SP system during opioid withdrawal in the rat. The enhanced production of SP1 -7 may reflect an increased release and/or metabolism of SP, which. ill tur n, counteracts the withdrawal. (C) 1998 Elsevier Science Ltd, All rights re served.