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Tolerance to the anticonvulsive effect of alcohol is not influenced by Pavlovian conditioning

University of British Columbia

The effects of environmental manipulations on the duration of kindled seizures elicited by amygdaloid stimulation were measured to determine if tolerance to the anticonvulsive effect of alcohol could be explained by the Pavlovian model of drug tolerance. Experiment 1 was conducted to determine if tolerance to the anticonvulsive effect of alcohol is context specific. Rats with kindled seizures received five bidaily alcohol injections in Environment A alternating with five bidaily saline injections in Environment B, each followed 1 hr later by an amygdaloid stimulation. On the test day, half the subjects received the test injection and stimulation in the alcohol-associated environment (Environment A) whereas the other half received the test injection and stimulation in the saline—associated environment (Environment B). No significant differences in seizure activity between the two groups were seen. The subjects receiving the test injection in Environment A were given saline injections and stimulations in this same environment 48 hr after the alcohol test injection. Exposure to just the alcohol-predictive cues did not elicit a compensatory increase in seizure activity as predicted from the Pavlovian model of drug tolerance. Experiment 2 was designed to show that extinction procedures would produce an attenuation of tolerance to the anticonvulsive effect of alcohol. Subjects were given bidaily alcohol injections and stimulations in Environment A for five sessions. The subjects in the extinction condition were then given five bidaily saline injections and stimulations in Environment A, whereas the control subjects were given only stimulations on these five days, but in an environment not associated with alcohol. On the test day, all subjects received an alcohol injection and stimulation in Environment A. Although the two groups did not differ significantly in seizure duration, they both exhibited seizure durations so close to zero that observing any further attenuation of tolerance in the group that had undergone the extinction procedures would not have been possible. Accordingly, it cannot be claimed that the extinction procedures affected tolerance to the anticonvulsive effect of alcohol, however the level of tolerance in the control group dissipated so rapidly that it is unlikely that learning played a role in its development. In Experiment 3, the effect of CS (conditioned stimuli) preexposure on the development of tolerance to the anticonvulsive effect of alcohol was investigated. Subjects in the Preexposure Group were given five bidaily saline injections and stimulations in Environment A — subsequently to be associated with alcohol administration. Control group subjects were given the same treatment but in Environment B. During the tolerance development sessions and the test session, all rats were given five bidaily alcohol injections and stimulations in Environment A. CS prexposure did not retard the development of tolerance to the anticonvulsive effect of alcohol. These results indicate that, tolerance to the anticonvulsive effect of alcohol can develop in the absence of conditioning effects. This study constitutes the first systematic demonstration of the failure to verify the Pavlovian model of tolerance« thus limiting the generality of the model.

Text

2010-05-29

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http://hdl.handle.net/2429/25200

Psychology

University of British Columbia

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