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  • Title: Effects of intracerebroventricular administration of beta-funaltrexamine on [3H]DAMGO binding to rat brain sections.
    Author: Martin TJ, Dworkin SI, Smith JE.
    Journal: J Pharmacol Exp Ther; 1993 Oct; 267(1):506-14. PubMed ID: 8229781.
    Abstract:
    In spite of an extensive body of knowledge regarding the pharmacological effects of centrally administered beta-funaltrexamine (beta-FNA), little is known about the distribution of mu opiate receptor alkylation produced by i.c.v. administration. This study examines the dose relationship between i.c.v. beta-FNA pretreatment and the affinity and density of mu opioid binding sites in discrete brain regions using in situ binding and quantitative receptor autoradiography. [3H]DAMGO binding was determined in coronal sections obtained from the frontal portion of the brain from animals 24 hr after i.c.v. administration of 0, 1, 5, 10, 20 or 40 nmol of beta-FNA. The Kd and Bmax values of [3H]DAMGO binding were unaltered in animals treated with saline or 1 nmol of beta-FNA, whereas treatment with 5, 10 and 20 nmol of beta-FNA increased Kd and decreased Bmax values. The 40 nmol dose did not affect the Kd but decreased the Bmax value. Administration of 40 nmol of beta-FNA i.c.v. was not found to affect either the Kd or Bmax of delta opioid receptors assessed with [3H]DPDPE. Although some brain regions appeared to be affected to a greater degree than others, the autoradiographic localization of [3H]DAMGO binding at 10 different brain levels revealed a generally homogeneous loss of binding after 40 nmol of beta-FNA. beta-FNA appears to alkylate mu opiate receptors throughout the brain after i.c.v. administration.
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