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Journal of Pharmacology And Experimental Therapeutics, Vol. 143, Issue 3, 309-313, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics

TOLERANCE TO BEHAVIORAL EFFECTS OF LSD-25 IN RAT

D. X. Freedman 1, J. B. Appel 1, F. R. Hartman 1, and M. E. Molliver 1

1 Psychopharmacology Laboratory, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut

The effects of LSD-25 on bar-pressing maintained by food reward, and tolerance to these effects, were investigated in the rat with two schedules of reinforcement, fixed-ratio (FR) and variable-interval (VI). With FR, the drug effect was defined by a period of no-responding; a gradual decline in response rate occurred on the interval schedule. The onset of behavioral disturbances began 4 to 8 minutes after i.p. injection and the duration depended upon dosage.

Tolerance was observed on both FR and VI within 7 to 8 days with daily doses at or below 130 µg of LSD-25/kg. It was characterized by a shortening of the time required for recovery from the maximal drug effect. The study of acute tolerance shows that partial tolerance develops rapidly (within 3 hours). With increased doses of LSD-25 tolerance to these effects on bar-pressing behavior is less likely to develop.

The importance of both behavioral and pharmacological variables in affecting both the response to LSD-25 and the development of tolerance was stressed.

Submitted on May 21, 1963
Accepted on October 23, 1963




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Copyright © 1964 by the American Society for Pharmacology and Experimental Therapeutics.