Cholecystokinin facilitates methamphetamine-induced dopamine overflow in rat striatum and fetal ventral mesencephalic grafts.
The purpose of this study was to investigate the interactions of sulfated (S) and unsulfated (US) cholecystokinin (CCK) and methamphetamine (MA)-induced dopamine (DA) overflow in rat striatum. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate extracellular DA concentration. CCK-8S, CCK-8US, MA, and DA were locally applied directly to the striatum of urethane-anesthetized Sprague-Dawley rats. We found that CCK potentiated MA-induced DA release in the anterior striatum. This response is probably mediated through CCK-A receptors because CCK-8S, but not CCK-8US, enhanced MA-induced responses. Replacement of Ca2+ with Mg2+ in the drug barrel antagonized this reaction, suggesting that the modulation of MA-induced DA release by CCK is Ca2+ dependent. Both MA-induced DA release and CCK modulatory effects disappeared in the striatum after unilaterally lesioning the medial forebrain boundle with 6-hydroxydopamine (6-OHDA). We had previously found that the zone of normalized dopamine clearance in 6-OHDA-lesioned rats was considerably larger than that of normalized release in the anterior striatum after fetal ventral mesencephalic (VM) transplantation, which may be a result of partial reinnervation from the transplant. In the present study, we found that the modulation of DA release by CCK was restored only in the zone of normalized release after fetal nigral transplantation; CCK did not increase MA-induced DA release throughout the larger partially innervated area. In conclusion, these findings suggest that not only DA release processes but also CCK modulatory mechanisms are restored in the anterior striatum after fetal VM transplantation.
Wang
Y
Y
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Perng
S L
SL
Lin
J C
JC
Tsao
W L
WL
D000818:Animals; D002421:Caudate Nucleus / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D004563:Electrochemistry; D016332:Fetal Tissue Transplantation; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D008694:Methamphetamine; D016627:Oxidopamine; D002766:Cholecystokinin; D004298:Dopamine