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Related Experiment Videos

Changes in dopamine-mediated behaviour during one year's neuroleptic administration.

A Clow, P Jenner, C D Marsden

    European Journal of Pharmacology
    |August 15, 1979
    PubMed
    Summary

    Long-term administration of trifluoperazine or thioridazine in rats reversed initial dopamine receptor blockade. Dopamine systems showed enhanced responses, leading to increased spontaneous behaviors despite continuous drug intake.

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    Area of Science:

    • Neuropharmacology
    • Behavioral Neuroscience

    Background:

    • Phenothiazine antipsychotics like trifluoperazine and thioridazine are known dopamine receptor antagonists.
    • Chronic administration of these drugs can lead to complex adaptive changes in the central nervous system.

    Purpose of the Study:

    • To investigate the long-term effects of trifluoperazine and thioridazine on dopamine system responsivity in a rodent model.
    • To determine if initial behavioral inhibitory effects of these antipsychotics are sustained or reversed with chronic exposure.

    Main Methods:

    • Male Wistar rats were administered trifluoperazine or thioridazine in drinking water for 12 months at high (2.5-40 mg/kg/day) and low (0.7-8 mg/kg/day) doses.
    • Behavioral assessments included catalepsy, spontaneous locomotion, apomorphine-induced stereotypy, and spontaneous mouth movements.

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    Main Results:

    • Initial catalepsy and locomotion inhibition resolved by 3 months.
    • Apomorphine-induced stereotypy initially decreased but was enhanced after 6 and 12 months of drug treatment.
    • A significant increase in spontaneous mouth movements was observed in drug-treated animals after 12 months.
    • Lower doses showed transient effects, but also led to increased spontaneous mouth movements at 12 months.

    Conclusions:

    • Chronic administration of trifluoperazine and thioridazine leads to a reversal of their initial dopamine receptor-blocking effects.
    • Cerebral dopamine systems demonstrate an enhanced response during continuous drug intake, suggesting adaptive plasticity.
    • These findings have implications for understanding long-term antipsychotic treatment and potential mechanisms of tardive dyskinesia.