PT  - JOURNAL ARTICLE
AU  - Jodie J. Rady
AU  - Gregory I. Elmer
AU  - James M. Fujimoto
TI  - Opioid Receptor Selectivity of Heroin Given Intracerebroventricularly Differs in Six Strains of Inbred Mice
DP  - 1999 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 438--445
VI  - 288
IP  - 2
4099  - http://jpet.aspetjournals.org/content/288/2/438.short
4100  - http://jpet.aspetjournals.org/content/288/2/438.full
SO  - J Pharmacol Exp Ther1999 Feb 01; 288
AB  - Heroin administered i.c.v. acts on supraspinal μ opioid receptors in ICR mice but on δ receptors in Swiss Webster mice. The purpose of this study was to determine the degree to which genotype plays a role in the opioid receptor selectivity of heroin across a range of fully inbred strains of mice. Six inbred strains were given heroin i.c.v. 10 min before the tail-flick test. Differences in the descending neurotransmitter systems involved in supraspinal opioid-induced analgesia were evaluated as the first step. Antagonism by bicuculline given intrathecally indicated the involvement of supraspinal δ receptors in activating spinal γ-aminobutyric acid (GABA) receptors; antagonism by intrathecal methysergide indicated either μ or κ receptor involvement. Antagonism by intrathecal yohimbine implicated μ and eliminated κ receptor involvement. Intracerbroventricular opioid antagonists (β-funaltrexamine, 7-benzylidenenaltrexone, naltriben, or nor-binaltorphimine) provided further differentiation. Based on these initial results, receptor selectivity was determined by more extensive ED50experiments with i.c.v. administration of heroin with opioid antagonists, β-funaltrexamine (for μ), naltrindole (for δ), and nor-binaltorphimine (for κ). The combined results indicated that heroin analgesia was predominantly mediated in C57BL/6J by δ, in DBA/2J and CBA/J by μ, and in BALB/cByJ and AKR/J by κ receptors. The response in C3H/HeJ appeared to involve μ receptors. The results indicate that the opioid receptor selectivity of heroin is genotype-dependent. Because these genotypes are fully inbred, the genetically determined molecular and neurochemical substrate mediating the different opioid receptor selectivities of heroin can be studied further. The American Society for Pharmacology and Experimental Therapeutics