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Comparative Study
. 2009 Oct;93(4):397-405.
doi: 10.1016/j.pbb.2009.06.001. Epub 2009 Jun 7.

Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis inbred rat strains: evidence for differential mu opioid receptor activation

Catherine M Davis  1 , Kenner C Rice, Anthony L Riley
Affiliations
Comparative Study

Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis inbred rat strains: evidence for differential mu opioid receptor activation

Catherine M Davis et al. Pharmacol Biochem Behav. 2009 Oct.

Abstract

The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0, 0.28, 0.90 and 1.60 mg/kg). Although (-)-U50,488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0, 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0, 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats.

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Figures

Figure 1
Figure 1
(A) Mean water consumption during the habituation phase for all F344 and LEW animals prior to conditioning with various doses of (−)-U50,488H. LEW animals consumed more water than the F344 rats on all days during this phase, except for days 7, 9 and 11. (B) Mean saccharin consumption across conditioning trials for all F344 (left panel) and LEW (right panel) animals receiving different doses of (−)-U50,488H or vehicle. * indicates saccharin consumption of animals conditioned with vehicle, 0.28, and 0.90 mg/kg was significantly higher than that of animals conditioned with 1.60 mg/kg. (C) Percent saccharin consumption (left panel) and total fluid consumption (right panel) for all animals conditioned with varying doses of U50,488H or vehicle. * denotes significant difference from animals receiving vehicle. # denotes significantly less saccharin consumed compared to animals receiving 0.28 mg/kg. ^ denotes significantly less saccharin consumed compared to animals receiving 0.90 mg/kg
Figure 2
Figure 2
(A) Mean water consumption during the habituation phase for all F344 and LEW animals prior to conditioning with various doses of SNC80. The LEW strain consumed more water on days 1-6, 8-9, and 12 compared to the F344 rats. Consumption was equivalent on all other days. (B) Mean saccharin consumption across conditioning trials for all F344 (left panel) and LEW (right panel) animals receiving varying doses of SNC80 or vehicle during aversion conditioning. * denotes saccharin consumption of animals conditioned with vehicle was significantly greater than consumption by all groups receiving SNC80. (C) Percent saccharin consumption (left panel) and total fluid consumption (right panel) for all animals conditioned with varying doses of SNC80 or vehicle. * denotes significant difference from vehicles (F344 and LEW).
Figure 3
Figure 3
(A) Mean water consumption during the habituation phase for all F344 and LEW animals prior to aversion conditioning with heroin. LEW animals consumed more water on each day of this phase, except for Day 7 when the consumption by the strains was equivalent. Note: some SE bars fall within the symbol on graph. (B) Mean saccharin consumption across conditioning trials for all F344 (left panel) and LEW (right panel) animals receiving varying doses of heroin or vehicle during aversion conditioning. * denotes consumption by vehicle groups (F344 and LEW) significantly greater than all F344 animals receiving heroin. + indicates saccharin consumption by the vehicle groups (F344 and LEW) significantly greater than LEW animals conditioned with 10 mg/kg heroin. # indicates that the LEW animals conditioned with 3.2 and 5.6 mg/kg consumed significantly more saccharin than all F344 animals conditioned with heroin (3.2, 5.6, and 10 mg/kg). † indicates a significant strain difference in saccharin consumption with all LEW animals conditioned with heroin (3.2, 5.6, and 10 mg/kg) drinking more saccharin than all F344 animals conditioned with heroin. Note: some SE bars fall within the symbol on the graph. (C) Percent saccharin consumption (left panel) and total fluid consumption (right panel) for the first (top) and second (bottom) two-bottle aversion test for all animals conditioned with varying doses of heroin or vehicle. *denotes significant difference from vehicle groups. + denotes significant strain differences at a specific dose of heroin.
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