Methodological problems in the analysis of behavioral tolerance in toxicology.

The analysis of selected data on differential behavioral tolerance to drugs and other chemicals leads to a series of tentative methodological proposals with potential interest for the purposes of toxicology. These data show a wide range of different relations between tolerance induced by continued exposure to treatment per se and tolerance dependent on specific treatment-behavior interactions, such as behavioral testing in the treatment state and unfavorable consequences on reinforcement density of response changes induced by treatment. Consequently, when tolerance phenomena occurring with a particular type of treatment deserve an in-depth analysis, a sequential strategy should assess (i) critical factors in short-term compensation for behavioral deficits (acute behaviorally augmented tolerance), (ii) relations between sensitization and tolerance phenomena (particularly in the case of agents with long-lasting and/or cumulative physiological-biochemical effects), with special regard to tolerance development in the absence of measurable changes in the lower dosage ranges, and (iii) factors responsible for behaviorally augmented tolerance in medium-and long-term experiments. The latter analysis may require the investigation of different relations between time of treatment and time of testing, and different treatment-induced changes in reinforcement density. Specific and non-specific transfer of coping responses across situations must also be considered, as well as changes in response topographies, interindividual differences in rate of tolerance development as a function of size and direction of the original treatment changes, and several other cues which can facilitate the understanding of the phenomena observed.(ABSTRACT TRUNCATED AT 250 WORDS)