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Behavioural and biochemical evidence for a long-lasting decrease in GABAergic function elicited by chronic

M G Corda, O Giorgi, G Biggio

    Brain Research
    |October 1, 1986
    PubMed
    Summary
    This summary is machine-generated.

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    Chronic FG 7142 treatment in rats caused long-lasting behavioral changes and reduced GABA receptors, suggesting a persistent down-regulation of GABAergic transmission in the central nervous system.

    Area of Science:

    • Neuroscience
    • Pharmacology

    Background:

    • Beta-carboline derivatives like FG 7142 are known psychoactive compounds.
    • GABAergic transmission plays a crucial role in central nervous system function.
    • Understanding the long-term effects of FG 7142 is important for its potential therapeutic or toxicological implications.

    Purpose of the Study:

    • To investigate the long-term neurochemical and behavioral effects of chronic FG 7142 administration in rats.
    • To determine if FG 7142 induces persistent changes in GABAergic neurotransmission.

    Main Methods:

    • Rats were chronically treated with FG 7142 (15 mg/kg i.p. twice daily for 10 days).
    • Behavioral tests (shock-induced suppression of drinking) were conducted up to 15 days post-treatment.
    • Seizure susceptibility to isoniazid was assessed after 25 days of withdrawal.

    Related Experiment Videos

  • GABA receptor binding assays ([3H]GABA) were performed on cerebral cortex and cerebellum homogenates at 5 and 15 days post-withdrawal.

    • Main Results:

    • Chronic FG 7142 induced a long-lasting proconflict effect (enhanced suppression of drinking) persisting for at least 15 days.
    • A significant sensitization to isoniazid-induced seizures was observed 25 days after withdrawal.
    • A 30% decrease in low-affinity GABA receptor density was found in the cerebral cortex and cerebellum.
    • High-affinity GABA receptor capacity and binding constants remained unchanged.

    Conclusions:

    • Chronic FG 7142 administration leads to persistent neurochemical and behavioral alterations.
    • The observed effects suggest a long-term down-regulation of GABAergic transmission in the central nervous system.
    • These findings highlight the potential for sustained impact of FG 7142 on neuronal function.