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Tolerance to the effects of baclofen and gamma-butyrolactone on locomotor activity and dopaminergic neurons in the mouse

G Gianutsos and KE Moore

Acute injections of baclofen or gamma-butyrolactone (GBL) into mice caused dose-dependent depression of locomotor activity and an elevation of the dopamine content and a reduction of dopamine turnover in the brain. An acute injection of baclofen, but not of GBL, was less effective in producing these effects in mice maintained on a diet containing baclofen for 10 to 12 days. This suggests that baclofen and GBL may influence dopamine neurons by different mechanisms. Acute injections of both baclofen and GBL were less effective in producing behavioral and neurochemical effects in mice pre-treated for 13 days with injections of GBL. Tolerance to the behavioral and neurochemical actions of baclofen and GBL do not appear to be the result of metabolic tolerance but possibly result from changes in the properties of the dopamine neurons.

Volume 207, Issue 3, pp. 859-869, 12/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics




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Pharmacokinetics and Pharmacodynamics of {gamma}-Hydroxybutyric Acid during Tolerance in Rats: Effects on Extracellular Dopamine
J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1252 - 1260.
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Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics.