The proposed research examines individual differences in male and female Long-Evans rats with regards to the hypothermic effects of a 4-hour steady-state administration of 60% nitrous oxide (N2O). Specifically, rats will be screened to identify those individual animals that are 1) initially insensitive to N2O induced-hypothermia, 2) initially sensitive to N2O-induced hypothermia but develop acute tolerance during the 4-hour administration, and 3) initially sensitive to N2O-induced hypothermia but show no evidence of acute tolerance development during the 4-hour administration. The overall objective is to identify individual difference characteristics that are apparent during an initial N2O administration and that will predict the way an individual will be affected over repeated N2O administrations. In the first experiment, population characteristics will be determined to provide a statistical basis for the assignment of screened rats into one of the 3 groups. Experiment 2 will compare the development of chronic (intercessional) tolerance among the rats assigned to groups based on their initial intra-sessional differences to N2O's effect. Tolerance is expected to develop with repeated exposure but the rate and magnitude of chronic tolerance development is hypothesized to differ according to group assignment. In the third experiment, rats in each group will receive N2O in association with a set of distinct environmental cues. This experiment will assess the role that classical conditioning plays in the expression of tolerance. Rats in the 3 different groups are hypothesized to differ in the conditioned responses that are acquired over repeated drug administrations. Differences in individual rat's unconditioned response to the effects of N2O distinguishes them from one another during the initial N2O administration and may account for differences between the animals with repeated N2O exposure. Female rats will be studied to ascertain whether the individual differences observed are similar to those observed for male rats. In all experiments, locomotor activity will be measured in addition to core body temperature to ascertain the generality of initial intra-sessional individual differences in predicting the subsequent effects of N2O. These studies have theoretical importance for understanding the mechanisms of drug tolerance as well as what accounts for individual differences in vulnerability to addiction and drug abuse.
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| Woods, S C; Ramsay, D S (2000) Pavlovian influences over food and drug intake. Behav Brain Res 110:175-82 |
