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.
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).
D000818:Animals; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*
D002090:Butyrophenones; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D008694:Methamphetamine; D013134:Spiperone; D004298:Dopamine