Self-administration cues as signals: Drug self-administration and tolerance

There is evidence that drug-associated exteroceptive cues elicit compensato ry conditional responses (CCRs) that contribute to tolerance. The authors e valuated whether interoceptive, self-administration cues (SACs) similarly c ontribute to tolerance. In Experiments 1 and 2, the ataxic effect of ethano l was measured in rats that self-administered (SA) ethanol-by either oral c onsumption or intragastric infusion-and in rats that were yoked (Y) to thes e self-administrators. In both experiments, the ataxic effect of ethanol wa s more pronounced in Y than in SA rats. In addition, SA rats failed to disp lay usual levels of tolerance when ethanol was administered in the absence of SACs and displayed a CCR of hypertaxia in response to SACs not followed by ethanol. The results of Experiment 3 indicate that the ataxic effect of intravenous heroin also was greater in Y than in SA rats. The findings sugg est that SACs contribute to drug tolerance.