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Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit

M O Carruba, G Nisticó, P Mantegazza

    Naunyn-Schmiedeberg'S Archives of Pharmacology
    |November 1, 1979
    PubMed

    Insights

    Chronic impairment of central nervous system (CNS) serotoninergic transmission may lead to receptor supersensitivity. This study in rabbits suggests that prolonged blockade of this system can indeed cause such changes.

    Area of Science:

    • Neuroscience
    • Pharmacology
    • Physiology

    Background:

    • Serotoninergic transmission plays a crucial role in CNS functions.
    • Understanding receptor sensitivity is vital for neurological drug development.

    Purpose of the Study:

    • To investigate if chronic impairment of CNS serotoninergic transmission leads to receptor supersensitivity.
    • To examine the hyperthermic responses to serotoninergic agonists after neuronal blockade.

    Main Methods:

    • Rabbits were pretreated with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) to impair serotoninergic transmission.
    • Hyperthermic responses to quipazine and 5-hydroxytryptophan (5-HTP) with a MAO inhibitor were measured.

    Main Results:

    • 5,6-DHT pretreatment potentiated hyperthermia induced by quipazine and 5-HTP (plus MAO inhibitor).
    • PCPA pretreatment enhanced quipazine-induced hyperthermia but inhibited the response to 5-HTP (plus MAO inhibitor).

    Conclusions:

    • Results suggest receptor supersensitivity following prolonged blockade of CNS serotoninergic neuronal transmission.
    • Differential effects indicate complex regulatory mechanisms within the serotoninergic system.

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