Alexa G Desko1, Jennifer L Cobuzzi, Anthony L Riley. 1. Psychopharmacology Laboratory, Department of Psychology, American University, 4400 Massachusetts Avenue NW, Washington, DC 20016, United States.
Abstract
BACKGROUND: The Lewis (LEW) and Fischer (F344) rat strains appear differentially sensitive to the aversive effects of several used and abused drugs. Naloxone, a mu opioid receptor antagonist that induces aversions in outbred rats but has no abuse potential, was assessed to determine the characteristics of compounds for which the strains differ. METHODS: Opioid-naïve male LEW and F344 rats were given access to saccharin followed by low (Experiment 1) and high (Experiment 2) doses of naloxone every 4th day for five pairings. Aversions were assessed in both one-bottle and two-bottle tests. RESULTS: In Experiment 1, aversions were evident at 10mg/kg (one-bottle) and at 5.6 and 10mg/kg (two-bottle) with no apparent strain difference for either assessment. In Experiment 2, aversions were evident for LEW animals (but not F344) at 18 and 32 mg/kg (one-bottle). LEW animals injected with 32 mg/kg displayed greater aversions than F344 animals receiving the same dose. Both strains displayed aversions at all doses in the two-bottle test with no strain difference. CONCLUSIONS: Naloxone induced aversions that were strain dependent only at specific doses and under the one-bottle testing condition. These results parallel those of several other used and abused drugs but differ dramatically from those seen with morphine in the two strains (F344>LEW). Further assessments utilizing the LEW-F344 model should investigate other drugs to establish the set of compounds for which the strains differ and to characterize the mechanism underlying the observed differences.
BACKGROUND: The Lewis (LEW) and Fischer (F344) rat strains appear differentially sensitive to the aversive effects of several used and abused drugs. Naloxone, a mu opioid receptor antagonist that induces aversions in outbred rats but has no abuse potential, was assessed to determine the characteristics of compounds for which the strains differ. METHODS: Opioid-naïve male LEW and F344 rats were given access to saccharin followed by low (Experiment 1) and high (Experiment 2) doses of naloxone every 4th day for five pairings. Aversions were assessed in both one-bottle and two-bottle tests. RESULTS: In Experiment 1, aversions were evident at 10mg/kg (one-bottle) and at 5.6 and 10mg/kg (two-bottle) with no apparent strain difference for either assessment. In Experiment 2, aversions were evident for LEW animals (but not F344) at 18 and 32 mg/kg (one-bottle). LEW animals injected with 32 mg/kg displayed greater aversions than F344 animals receiving the same dose. Both strains displayed aversions at all doses in the two-bottle test with no strain difference. CONCLUSIONS:Naloxone induced aversions that were strain dependent only at specific doses and under the one-bottle testing condition. These results parallel those of several other used and abused drugs but differ dramatically from those seen with morphine in the two strains (F344>LEW). Further assessments utilizing the LEW-F344 model should investigate other drugs to establish the set of compounds for which the strains differ and to characterize the mechanism underlying the observed differences.