An assessment with morphine of the relation between reward sensitization and the development of the UCS preexposure effect in aversion learning

Conditioned Taste Aversion (CTA) is thought to be a behavioral index of toxicity. After pairings of a distinctive solution and a drug (unconditioned stimulus; UCS) injection, animals will avoid consumption of the solution, and this avoidance is thought to reflect the aversive effects of this compound. Preexposure to this compound can result in an attenuation of CTA, referred to as the UCS preexposure effect in taste aversion learning. Although CTA can occur with a variety of unconditioned stimuli (UCS), it has been argued that reward sensitization may best explain the UCS preexposure effect with morphine given that morphine preexposure enhances morphine conditioned place preferences (CPP) (i.e., measure of drug reward). To address this possibility, the present study was designed to provide a comprehensive empirical examination of whether enhanced morphine-CPP developed concurrently with the UCS preexposure effect with morphine. This may be best accomplished using a combined CTA/CPP procedure, to assess these effects within the same animals under identical preexposure conditions. In Experiment 1, the simultaneous development of CTAs and CPPs in this combined procedure was assessed, where subjects received saccharin or water followed by morphine-injection (5 mg/kg; subcutaneous) and were then placed into one of two distinctive CPP compartments. The following day they received the other solution followed by drug vehicle-injection and then placed into the other CPP compartment. This two-day cycle was repeated four times after which a CPP test and CTA test revealed place preferences and taste aversions conditioned from the same morphine injection within the same animals. In Experiment 2, the effects of morphine preexposure (0 or 5 mg/kg; 5 subcutaneous injections every second day) on CTA and CPP (conditioned with 1 or 5 mg/kg; subcuntaneous) were assessed. There were four conditioning cycles (see Experiment 1), each followed by a CTA and CPP test. Morphine conditioned both a CTA and a CPP in a dose-related manner. Interestingly, morphine preexposure both attenuated CTAs (UCS preexposure effect) and enhanced CPPs in a parallel fashion. These results are consistent with a reward sensitization interpretation of the UCS preexposure effect with CTA; however, alternate interpretations are discussed.