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Related Experiment Videos

Chronic haloperidol does not increase specific dopamine receptor binding in rat frontal cortex

E Meller, K Bohmaker, H Rosengarten

    Research Communications in Chemical Pathology and Pharmacology
    |September 1, 1982
    PubMed
    Summary

    Chronic neuroleptic treatment did not alter dopamine D2 receptor binding in rat frontal cortex. However, this treatment significantly increased dopamine receptor binding in the striatum, suggesting regional differences in neuroleptic tolerance.

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    Area of Science:

    • Neuroscience
    • Pharmacology
    • Receptor Binding Assays

    Background:

    • Dopamine receptors, particularly D2, are crucial targets for antipsychotic medications.
    • Neuroleptic treatments can lead to adaptive changes in dopamine receptor systems.
    • Previous research suggests regional differences in neuroleptic effects, with the frontal cortex showing resistance to certain adaptations.

    Purpose of the Study:

    • To investigate the effect of chronic haloperidol treatment on dopamine D2 receptor binding in rat frontal cortex and striatum.
    • To determine if the frontal cortex exhibits resistance to neuroleptic-induced changes in dopamine receptor binding.

    Main Methods:

    • Utilized [3H]spiroperidol radioligand binding assays to quantify dopamine D2 receptor binding.
    • Administered chronic haloperidol at two different doses and durations (0.5 mg/kg for 3 weeks; 2.5 mg/kg for 5 weeks) to rats.

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  • Employed sulpiride as a specific D2 dopamine receptor antagonist to measure specific binding.

    • Main Results:

    • Chronic haloperidol treatment did not alter specific [3H]spiroperidol binding to dopamine receptors in the rat frontal cortex.
    • Both chronic haloperidol treatment regimens significantly increased specific [3H]spiroperidol binding to dopamine receptors in the rat striatum.
    • These findings indicate a regional dissociation in the neuroadaptive response to chronic haloperidol.

    Conclusions:

    • The rat frontal cortex dopamine system appears resistant to the upregulation of D2 receptors typically observed with chronic neuroleptic administration.
    • The striatum shows a significant increase in dopamine D2 receptor binding following chronic haloperidol treatment.
    • These results support the hypothesis of differential neuroleptic tolerance development between the frontal cortex and striatum.