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Rech RH, Lyness WH, Moore KE, Commissaris RL. 
“Behavioral Tolerance To The Effects Of LSD In Rats”. 
Federation Proc.. 1980;39(3, Part II):1095.
Tolerance to the behavioral effects of LSD in animals has been reported to occur after only a short period of repeated administration. Winters (1971) has shown that this tolerance is not dispositional in nature. While tolerance to the behavioral effects of LSD are demonstrable, concomitant biochemical changes indicative of pharmacodynamic (cellular) tolerance have not been observed. In the present study food-deprived male rats were trained to press a bar in one of four standard operant chambers for food reinforcement. The schedule controlling this behavior was gradually extended to Fixed Ratio-40 (FR-40; every 40th response produces a 45 mg food pellet). Administration of 100 mcg/kg immediately before the start of the operant session resulted in cessation of responding for some portion of the 40-min test session ("hallucinatory pause"). Four successive days of LSD administration prior to the start of the behavioral session decreased the response to LSD on each suceeding day (tolerance). However, when 100 mcg/kg LSD was given to these same animals on four successive days immediately after completion of the operant session, no tolerance was observed on day 5 when LSD was given before the start of the session. These data suggest that, with this particular dosing regimen and behavioral test, a large portion of the tolerance observed following repeated LSD administration is behavioral.
Notes # : Abstr. No. 4357
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