Abstract
The use of d-amphetamine pellet implantation as a method for producing rapid central drug tolerance was investigated. Mice were implanted with d-amphetamine pellets containing 2 mg of drug and were challenged 24 h later, a time when no detectable drug was present, with various doses of d-amphetamine i.p. Implantation was found to potentiate the stereotyped activity and produced tolerance to the exploratory activity induced by d-amphetamine. Daily pellet implantation for 3 days was not found to produce tolerance to the stereotyped activities. Animals administered a single pellet showed no difference in the brain disposition or metabolism of a subsequent dose of 3H-d-amphetamine. Twenty-four hour pellet implantation markedly increased the rate of conversion of 3H-tyrosine to 3H-dopamine (330%) and 3H-norepinephrine (61%) in the subcortex. However, this effect was reversed by the administration of 10 mg/kg of d-amphetamine.
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This work represents a portion of the dissertation submitted to the College of Pharmacy, Wayne State University, by R. J. Hitzemann in partial fulfillment of the requirements for the degree of Master of Science.
This work was supported in part by USPHS Grants MH-11846 (EFD) and MH-20559 (HHL).
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Hitzemann, R.J., Loh, H.H., Craves, F.B. et al. The use of d-amphetamine pellet implantation as a model for d-amphetamine tolerance in the mouse. Psychopharmacologia 30, 227–240 (1973). https://doi.org/10.1007/BF00422869
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DOI: https://doi.org/10.1007/BF00422869