Age and strain differences in morphine-induced taste aversions: A behavioral and neurochemical assessment

Drugs of abuse have both rewarding and aversive effects with the relative balance of these two effects determining their subsequent use and abuse. Understanding this balance and the various factors that might impact it may provide insight into drug use and abuse. In this context, the inbred LEW and F344 rat strains have been shown to differ in their sensitivity to the aversive effects of a host of drugs of abuse, including morphine. Although strain-dependent differences in morphine-induced aversions have been well characterized, these effects have been limited to adults and it is not known whether such effects are evident in adolescents and are developmentally stable or if such differences are manifested only in adulthood as a function of some developmental history. To address these possibilities, adolescent F344 and LEW rats were given access to a novel saccharin solution and subcutaneously injected with various doses of morphine (0, 3.2, 10 and 18 mg/kg). This procedure was repeated for four conditioning cycles following which all subjects were given access to water and saccharin in a two-bottle test of the aversion. To determine if morphine brain levels differed between the two strains and if any differences were related to strain differences in aversion learning, subjects were given an injection of the dose of morphine administered during conditioning and brain morphine levels were assessed with high-performance liquid-chromatography. Both adolescent and adult F344 subjects exhibited robust morphine-induced taste aversions at all doses tested, while the LEW subjects were relatively insensitive to the aversive properties of morphine, suggesting that the differential sensitivity to the aversive effects of morphine between the strains is highly heritable and developmentally stable. In addition, adolescents (averaged across strain) displayed weaker aversions that adults. Both adolescent and adult subjects displayed dose-dependent differences in brain morphine levels with the levels significantly lower in LEW adolescents relative to the F344 counterparts. None of these levels was associated with the reported differences in aversion learning. The basis for the strain differences in morphine-induced aversions was discussed in relation to possible peripheral and central mechanisms mediating and modulating the aversive effects of morphine.