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

The Lewis, Fischer 344, Brown Norway, Spontaneously Hypertensive, and Wista r-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.). T he lethal properties of the amphetamine were recorded within 24 h after its administration whereas neurotoxicity (as assessed by frontocortical 5-hydr oxytryptamine (5-HT) reuptake and 5-HT transporter binding assays) was anal yzed 1 week after PCA administration. Preliminary experiments indicated tha t neither the rapid hyperlocomotor and/or the hypoexploratory effect of PCA nor the in vitro potency of PCA to inhibit frontocortical [H-3]5-HT reupta ke varied between strains. On the other hand, strain differences were obser ved with respect to the rapid fatal effects of the 5 and 10 mg/kg doses of PCA administration. Lastly, frontocortical [H-3]5-HT reuptake and [H-3]cita lopram binding at 5-HT transporters diminished in a dose-dependent, but str ain-independent, manner 1 week after the acute injection of PCA. This study reveals an independency between the mechanisms underlying the fatal effect s of PCA on the one hand, and the longterm damaging effects of PCA on serot onergic neurons on the other hand. (C) 2001 Elsevier Science Ireland Ltd. A ll rig hts reserved.