These studies were undertaken to determine the effects of mu-opioid receptor depletion through irreversible alkylation on the dose-effect curve for heroin self-administration. Heroin maintained responding in rats with an inverted U-shaped dose-effect curve and administration of 10 nmol of beta-funaltrexamine i.c.v. (beta-FNA) significantly increased the ED50 on the ascending limb from 1.9 to 5.3 micrograms/infusion, and from 24.3 to 211.8 micrograms/infusion on the descending limb. Administration of saline i.c.v. produced no effect on heroin self-administration. Administration of 40 nmol of beta-FNA increased the ED50S from 5.1 to 33.9 and from 14.4 to 502.8 micrograms/infusion on the ascending and descending portions of heroin's dose-effect curve, respectively. beta-FNA (40 nmol, i.c.v.) had no effect on cocaine self-administration. [3H]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-administration were completely overcome by increasing the dose of heroin however, as the shape and slope of the self-administration dose-effect curve was not different when higher doses of heroin were made available for self-administration compared to control data or saline administration. Therefore, there appear to be spare mu-opioid receptors for heroin for the production of its reinforcing effects in rats. Furthermore, the self-administration dose-effect curves returned to control values prior to the return of [3H]DAMGO binding, further suggesting that the full complement of mu-opioid receptors is not necessary for heroin to produce its reinforcing effects. These findings support the existence of spare mu-opioid receptors for heroin in maintaining self-administration in rats.
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|Titolo:||Effects of β-Funaltrexamine on dose-effect curves for heroin self-administration in rats: comparison with alteration of (3 H)DAMGO binding to rat brain sections|
|Rivista:||DRUG AND ALCOHOL DEPENDENCE|
|Citazione:||Martin, T.j., DE MONTIS, M.G., Kim, S.a., Sizemore, G.m., Dworkin, S.i., & AND SMITH, J.e. (1998). Effects of β-Funaltrexamine on dose-effect curves for heroin self-administration in rats: comparison with alteration of (3 H)DAMGO binding to rat brain sections. DRUG AND ALCOHOL DEPENDENCE, 52, 135-147.|
|Appare nelle tipologie:||1.1 Articolo in rivista|