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 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 [(3)H]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 [(3)H]5-HT reuptake and [(3)H]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.
Fernandez
F
F
NeuroGénétique et Stress, INSERM U471-INRA, Institut F. Magendie, Rue Camille Saint-Saëns, 33077 Cédex, Bordeaux, France.
Aguerre
S
S
Mormède
P
P
Chaouloff
F
F
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015283:Citalopram / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D013045:Species Specificity; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D015283:Citalopram; D012701:Serotonin; D010133:p-Chloroamphetamine