Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. I. Biochemical and behavioral analysis

Judith L. Steinman, Susan M. Carlton, Bernard Haber, William D. Willis

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    The involvement of endogenous serotonergic pathways in the mediation of antinociception has been indicated by electrophysiological, pharmacological and behavioral experiments. However, manipulation of the indole pathway, either by lesioning of raphe nuclei or drug intervention, often produces disparate results. In particular, serotonin (5-HT) synthesis inhibition with p-chlorophenylalanine (PCPA) has been reported to produce either hyperalgesia or analgesia, depending upon the type of pain measurement examined. In the present study, we sought to evaluate the effects of PCPA on (1) behavioral responses to noxious stimulation, and (2) levels of serotonin, tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in raphe nuclei (pallidus, obscurus, magnus and dorsalis) and spinal cord regions by HPLC with electrochemical detection. Treatment of rats with 400 or 600 mg/kg of PCPA for 3 consecutive days resulted in significant elevations in pain thresholds assessed by tail withdrawal from radiant heat as well as vocalization to electric shock of the tail. The effect of PCPA on vocalization threshold was particularly striking, for the majority of animals showed a nociceptive-specific attenuation of this response. Although the PCPA induced changes in indole content of the various raphe nuclei were not unequivocally dose-dependent, differential reductions of serotonin and 5-HIAA were clearly detected in the various raphe regions. Nuclei raphe pallidus and obscurus were depleted of 5-HT and 5-HIAA to the greatest extent, whereas levels detected in nuclei raphe magnus and dorsalis were reduced by 30-40% from control values. Metabolism of 5-HT and 5-HIAA appeared unaffected by PCPA in all regions examined except the dorsal portion of the spinal cord. These findings collectively suggest that the effects of PCPA are not uniform throughout the central nervous system and raise the possibility that discrepancies in the behavior literature may be attributed to drug-induced changes in some, but not all serotonergic pathways.

    Original languageEnglish (US)
    Pages (from-to)297-309
    Number of pages13
    JournalBrain Research
    Volume426
    Issue number2
    DOIs
    StatePublished - Nov 24 1987

    Fingerprint

    Fenclonine
    Brain Stem
    Spinal Cord
    Serotonin
    Hydroxyindoleacetic Acid
    Raphe Nuclei
    Tail
    Pain Threshold
    Hyperalgesia
    Pain Measurement
    Tryptophan
    Pharmaceutical Preparations
    Analgesia
    Shock
    Central Nervous System
    Hot Temperature
    High Pressure Liquid Chromatography
    Pharmacology

    Keywords

    • Analgesia
    • Dorsal spinal cord
    • Electrochemical detection
    • Motoneuron
    • Nociception
    • p-Chlorophenylalanine
    • Raphe nucleus
    • Serotonin

    ASJC Scopus subject areas

    • Developmental Biology
    • Molecular Biology
    • Clinical Neurology
    • Neuroscience(all)

    Cite this

    Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. I. Biochemical and behavioral analysis. / Steinman, Judith L.; Carlton, Susan M.; Haber, Bernard; Willis, William D.

    In: Brain Research, Vol. 426, No. 2, 24.11.1987, p. 297-309.

    Research output: Contribution to journalArticle

    Steinman, Judith L. ; Carlton, Susan M. ; Haber, Bernard ; Willis, William D. / Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. I. Biochemical and behavioral analysis. In: Brain Research. 1987 ; Vol. 426, No. 2. pp. 297-309.
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