Elsevier

Neuroscience Letters

Volume 297, Issue 1, 5 January 2001, Pages 53-57
Neuroscience Letters

Differential sensitivities to the lethal, but not the neurotoxic, effects of p-chloroamphetamine in inbred rat strains

https://doi.org/10.1016/S0304-3940(00)01667-0Get rights and content

Abstract

The Lewis, Fischer 344, Brown Norway, Spontaneously Hypertensive, and Wistar–Kyoto inbred rat strains were, respectively, compared for the lethal and neurotoxic effects of acute p-chloroamphetamine (PCA, 2.5–10 mg/kg i.p.). The lethal properties of the amphetamine were recorded within 24 h after its administration whereas neurotoxicity (as assessed by frontocortical 5-hydroxytryptamine (5-HT) reuptake and 5-HT transporter binding assays) was analyzed 1 week after PCA administration. Preliminary experiments indicated that neither the rapid hyperlocomotor and/or the hypoexploratory effect of PCA nor the in vitro potency of PCA to inhibit frontocortical [3H]5-HT reuptake varied between strains. On the other hand, strain differences were observed with respect to the rapid fatal effects of the 5 and 10 mg/kg doses of PCA administration. Lastly, frontocortical [3H]5-HT reuptake and [3H]citalopram binding at 5-HT transporters diminished in a dose-dependent, but strain-independent, manner 1 week after the acute injection of PCA. This study reveals an independency between the mechanisms underlying the fatal effects of PCA on the one hand, and the long-term damaging effects of PCA on serotonergic neurons on the other hand.

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Acknowledgements

The authors wish to thank Yannick Mellerin for taking care of the animals, and La Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie for financial support.

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