Selective unilateral inactivation of striatal D1 and D2 dopamine receptor subtypes by EEDQ: turning behavior elicited by D2 dopamine receptor agonists.
The unilateral intrastriatal injection of the irreversible dopamine (DA) receptor blocker N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) induces a marked decrease in the density of D1 (-48%) and D2 (-51%) DA receptors available for binding to [3H]SCH 23390 and [3H]raclopride, respectively. A challenge dose of the D2 agonist LY 171555 (1 mg/kg, i.p., 24 h after EEDQ) causes intensive ipsiversive circling behavior, whereas the selective D1 agonist SKF 38393 (20 mg/kg, i.p., 24 h after EEDQ) is unable to induce rotations. The density of D1 and D2 DA receptors returns to basal levels by 7 days after the intrastriatal infusion of EEDQ. This biochemical recovery is associated with a progressive decrease in the number of rotations elicited by a challenge dose of LY 171555, suggesting that EEDQ does not cause any relevant neuronal damage. A selective inactivation of striatal D1 or D2 DA receptors can be obtained by injecting EEDQ 30 min after the administration of the D2 antagonist raclopride (20 mg/kg, i.p.) or of the D1 antagonist SCH 23390 (2 mg/kg, s.c.), respectively. The intensity of the circling behavior induced by LY 171555 24 h after EEDQ in animals with a selective inactivation of D2 DA receptors is similar to that found in rats in which both D1 and D2 DA receptors have been inactivated. In contrast, LY 171555 does not cause rotations when the density of D1 DA receptors is selectively decreased by EEDQ in rats pretreated with raclopride.(ABSTRACT TRUNCATED AT 250 WORDS)
Giorgi
O
O
Department of Experimental Biology, University of Cagliari, Italy.
Biggio
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D019257:Quinpirole; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012399:Rotation; D012457:Salicylamides / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011804:Quinolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D015016:Yohimbine; D020891:Raclopride; C000470:EEDQ; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007650:Ketanserin; D011224:Prazosin