EFFECTS OF BETA-FUNALTREXAMINE ON DOSE-EFFECT CURVES FOR HEROIN SELF-ADMINISTRATION IN RATS - COMPARISON WITH ALTERATION OF [H-3]DAMGO BINDING TO RAT-BRAIN SECTIONS

These studies were undertaken to determine the effects of mu-opioid re ceptor depletion through irreversible alkylation on the dose-effect cu rve for heroin self-administration. Heroin maintained responding in ra ts with an inverted U-shaped dose-effect curve and administration of 1 0 nmol of beta-funaltrexamine i.c.v. (beta-FNA) significantly increase d the ED50 on the ascending limb from 1.9 to 5.3 mu g/infusion, and fr om 24.3 to 211.8 mu g/infusion on the descending limb. Administration of saline i.c.v. produced no effect on heroin self-administration. Adm inistration of 40 nmol of beta-FNA increased the ED(50)s from 5.1 to 3 3.9 and from 14.4 to 502.8 mu g/infusion on the ascending and descendi ng portions of heroin's dose-effect curve, respectively. beta-FNA (40 nmol, i.c.v.) had no effect on cocaine self-administration, [H-3]DAMGO binding density was decreased in the caudate and nucleus accumbens by 29 or 54% 24 h after administration of 10 or 40 nmol of beta-FNA i.c. v., respectively. The effects of beta-FNA on heroin self-administratio n were completely overcome by increasing the dose of heroin however, a s the shape and slope of the self-administration dose-effect curve was not different when higher doses of heroin were made available for sel f-administration compared to control data or saline administration. Th erefore, there appear to be spare mu-opioid receptors for heroin for t he production of its reinforcing effects in rats. Furthermore, the sel f-administration dose-effect curves returned to control values prior t o the return of [H-3]DAMGO binding, further suggesting that the full c omplement of mu-opioid receptors is not necessary for heroin to produc e its reinforcing effects. These findings support the existence of spa re mu-opioid receptors for heroin in maintaining self-administration i n rats. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.