There is increasing evidence that some aspects of drug tolerance are significantly influenced by environmental context and experimental contingencies. The proposed investigations are designed to evaluate the role of learning mechanisms in morphine tolerance acquisition. Experiment 1 is intended to reveal the effects of dosage and environmental context on behaviorally augmented tolerance. Extinction manipulations and exposure to a novel environment under morphine will be used to assess whether augmented tolerance results from specific environment-drug association. The measure of tolerance, shock analgesia, will be determined using a computerized jump/flinch apparatus. Experiment 2 is designed to reveal whether flavors can elicit behaviorally augmented morphine tolerance. Thus, during tolerance development rats will differ on the basis of the correlation of environmental and/or flavor cues with morphine delivery. Shock analgesia and flavor intake will serve as dependent measures. Experiment 3 is designed to reveal whether contextual cues per se can elicit behaviorally augmented ethanol (EtOH) tolerance. In addition, this study should reveal whether a history of activation or stress under EtOH enhances augmented tolerance and whether environmental context affects blood EtOH clearance rates. Experiment 4 is designed to reveal whether behavioral manipulations result in enhanced tolerance after prolonged exposure to high morphine dosages. High and low dosage animals will be given shock analgesia tests at the same low test dosage to provide a standard comparison and to reveal conditioned inhibition of morphine tolerance. Lastly, Experiment 5 is designed to reveal UCS preexposure or Kamin blocking effects in morphine tolerance acquisition. Such effects would be antagonistic to a nonassociative explanation of morphine tolerance development. Rectal temperature will serve as the tolerance measure; the results show whether temperature responses are counteradaptive to direct drug effects.
NIH ExPorter
NIH ExPorter