Morphine-induced place conditioning in Fischer and Lewis rats: Acquisition and dose-response in a fully biased procedure

Abstract

The Fischer (F344) and Lewis (LEW) rat strains differ on a variety of behavioral assays examining the effects of morphine, with many of the differences observed during acquisition of behavioral responses. The results of these studies and others examining endogenous physiology and the biochemical effects of morphine suggest that F344 rats are more sensitive to morphine than LEW rats. However, LEW animals have shown greater conditioned place preferences (CPP) to 4 mg/kg than F344 rats. CPP is a popular assay of drug reward in which acquisition of the preference can be measured across multiple conditioning cycles, yet this aspect of CPP has not been assessed in F344 and LEW rats. As part of an ongoing effort to fully characterize the conditioned rewarding effects of abused drugs in these strains, the present study assessed the effects of 0, 1, 4 and 10 mg/kg subcutaneous (SC) morphine in adult male F344 and LEW rats ( n = 12/strain/dose). A fully biased place conditioning procedure was employed where morphine's effects were paired with the initially non-preferred chamber on Day 1, saline was paired with the preferred chamber on Day 2 and drug-free access to the entire apparatus was allowed on Day 3. This conditioning and testing regimen was repeated for four consecutive cycles. The F344 animals acquired CPP at 1 mg/kg only; this effect emerged after only two conditioning cycles. LEW rats never acquired a CPP at any dose tested. Peak blood morphine levels following SC injections of 1, 4 or 10 mg/kg revealed no significant strain or dose effects. These behavioral data are consistent with the hypothesis that F344 rats are more sensitive to the rewarding effects of morphine than LEW rats. Additional implications for the Fischer–Lewis model of drug abuse and the utility of CPP acquisition procedures are discussed.