A high dose of EEDQ reduces pituitary dopamine D2 receptor density and the prolactin suppressive potency of agonists.
In male rats, a high dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 30 mg/kg s.c., 24 h) caused a reduction of pituitary dopamine D2 receptor density by 27% as measured by means of in vivo radioligand binding (using a single dose of the ligand [3H]spiperone). The same dose of EEDQ reduced the potency, but not the maximal response, of the dopamine D2 receptor agonists R-(-)-N-n-propylnorapomorphine (NPA), (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP), and 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5]azepine (B-HT 920) with respect to suppression of prolactin release after pretreatment with gamma-butyrolactone. The measured reduction in dopamine D2 receptor density after EEDQ was of the same magnitude as the reduction in receptor number predicted from the EEDQ induced shift in the dose-response curve of the full dopamine D2 receptor agonist NPA. The findings are discussed in relation to our previous observation that a somewhat lower dose of EEDQ (20 mg/kg s.c., 24 h) effectively reduces the efficacy of partial dopamine D2 receptor agonists while affecting neither the prolactin response to full dopamine D2 receptor agonists nor the density of pituitary dopamine D2 receptors.
Ekman
A
A
Department of Pharmacology, University of Göteborg, Sweden.
Eriksson
E
E
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000187:drug effects*
D001381:Azepines; D015259:Dopamine Agents; D010880:Piperidines; D011804:Quinolines; D017448:Receptors, Dopamine D2; C000470:EEDQ; C024763:talipexole; D011388:Prolactin; C026539:preclamol