Increased dopamine D2(High) receptors in amphetamine-sensitized rats, measured by the agonist [(3)H](+)PHNO.
Repeated injections of amphetamine causes animals to become sensitized and supersensitive to DA. Previous work showed that the striata from such sensitized rats revealed a 3.5-fold increase in the density of D2(High) DA receptors, as measured by the guanine-nucleotide-sensitive component of [(3)H]raclopride binding. The present study was done to confirm these earlier findings by different methods and different ligands. The striata from amphetamine-sensitized rats showed an increase of 2.2-fold in the density of guanine-nucleotide-sensitive D2 receptors labeled by saturation experiments with [(3)H](+)PHNO. The proportion of D2(High) receptors was also found to increase 2.5-fold using the method of competition between DA and [(3)H]domperidone. The overall 2.2-3.5-fold increase of DA D2(High) receptors may explain why amphetamine-sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased.
Seeman
Philip
P
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada. philip.seeman@utoronto.ca
McCormick
Patrick N
PN
Kapur
Shitij
S
D018663:Adrenergic Agents / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D018663:Adrenergic Agents; D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; C042631:naxagolide; D000661:Amphetamine; D004298:Dopamine