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  • Title: Lasting changes in high affinity 3H-spiperone binding to the rat striatum and mesolimbic area after chronic methamphetamine administration: evaluation of dopaminergic and serotonergic receptor components.
    Author: Akiyama K, Sato M, Kashihara K, Otsuki S.
    Journal: Biol Psychiatry; 1982 Dec; 17(12):1389-402. PubMed ID: 7159638.
    Abstract:
    The presence of high and low affinity 3H-spiperone binding sites was demonstrated in both the rat striatum and mesolimbic area. Dopaminergic receptor component was displaced by 10 microM 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), and serotonergic receptor component by 0.2 microM mianserin. Dopaminergic receptor component was saturated at less than the range of ligand concentrations labeling the high-affinity binding sites. Treatment with 4 mg/kg of methamphetamine (MAP) for 14 days, followed by a 7-day drug-free period, resulted in significant changes in the maximal number of binding sites (Bmax) at the high-affinity sites (an increase in the mesolimbic area and a decrease in the striatum), but no significant changes in Bmax at the low affinity sites. The long-lasting increase in mesolimbic Bmax at the high-affinity 3H-spiperone binding site may be an underlying basis for MAP-induced behavioral hypersensitivity (reverse tolerance).
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