Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide.
Groups of rats administered cocaine-HC1 (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [3H]DA, modulation of [3H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [3H]spiperone binding assays.
Dwoskin
L P
LP
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Peris
J
J
Yasuda
R P
RP
Philpott
K
K
Zahniser
N R
NR
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists; D008297:Male; D010479:Pergolide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D010479:Pergolide; D013134:Spiperone; D003042:Cocaine