A HIGH-DOSE OF EEDQ REDUCES PITUITARY DOPAMINE-D(2) 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 red uction of pituitary dopamine D2 receptor density by 27% as measured by means of in vivo radioligand binding (using a single dose of the liga nd [H-3]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-propylpiperidi ne ((+)-3-PPP), and 2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5]azepine (B-HT 920) with respect to suppression of prolactin release after pre treatment with gamma-butyrolactone. The measured reduction in dopamine D2 receptor density after EEDQ was of the same magnitude as the reduc tion in receptor number predicted from the EEDQ induced shift in the d ose-response curve of the full dopamine D2 receptor agonist NPA. The f indings are discussed in relation to our previous observation that a s omewhat lower dose of EEDQ (20 mg/kg s.c., 24 h) effectively reduces t he efficacy of partial dopamine D2 receptor agonists while affecting n either the prolactin response to full dopamine D2 receptor agonists no r the density of pituitary dopamine D2 receptors.