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Freedman DX, Aghajanian GK.
“Time parameters in acute tolerance, cross tolerance, and antagonism to psychotogens.”.
Federation Proc.. 1959;18:390.
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Abstract
"Specification of time intervals is critical for the study of neuro-receptor processes underlying tolerance. Doses of LSD-25 and mescaline producing immediate onset of a 45' impairment in the rope-climbing of rats were found; if doses are at 24 hour intervals, 3-4 days are required for complete chronic tolerance (Freedman et al. Science 127: 1173, 1958). If doses are at 1-6 hour intervals after the initial dose, complete acute tolerance develops to the 45' effect of each drug. The ergot series has unique properties. BOL-148 yields no impairment; prevents it if given with either drug; antagonizes it if given during the 45' period. LSD-25 enhances impairment of LSD-25 or mescaline if given during the 45' period but prevents it if given 1-6 hours after either psychotogen. Thus, rats acutely or chronically tolerant to LSD-25 are tolerant to mescaline, but cross-tolerance is one way since mescaline-tolerant rats show enhanced response to LSD- 25. Differences between acute and chronic tolerance and importance of the initial dose are shown. Doses producing acute tolerance have no effect on development of the chronic type; the critical interval (between 8-22 hours) differentiating the two will be cited. Since findings do not hold for all behavioral and autonomic effects of psychotogens, factors determining the rope-climbing effect will be discussed.
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| Notes # : (Amer. Soc. for pharmacol. & exp. therap., Atlantic City, NJ, Apr 13-17, 1959) |
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