TY - JOUR
T1 - The distribution of cocaine in mice differs by age and strain
AU - McCarthy, Lois E.
AU - Mannelli, Paolo
AU - Niculescu, Michelle
AU - Gingrich, Kevin
AU - Unterwald, Ellen M.
AU - Ehrlich, Michelle E.
N1 - Funding Information:
This research was supported by ME 02-177 (M.E.E.) from the Commonwealth of Pennsylvania and by NIH NS41871 (M.E.E. and E.M.U.). The authors wish to acknowledge the expertise of Matthew M. McMullin, DABFT, TC(NRCC) (National Medical Services, Willow Grove, PA), in the GC/MS analysis of cocaine and BZE concentrations.
PY - 2004
Y1 - 2004
N2 - Few studies have examined the influence of the age and the strain of mouse on the pharmacokinetics of psychostimulants, or the role of pharmacokinetics in age-related differences in drug responses. The present study compared concentrations of cocaine, and its metabolite, benzoylecgonine (BZE), in the blood and brain of early (P35) and later (P42) periadolescent and adult (P63) CD-1 and C57BL/6 male mice 15 min after acute intraperitoneal injection of cocaine (20 mg/kg). Brain levels of cocaine and BZE after seven daily cocaine injections in CD-1 and C57BL/6 mice beginning on P35 and on P63 were also measured. P35 periadolescents of both strains had lower blood cocaine levels than did the adults, but only C57BL/6 periadolescents had lower brain cocaine levels than the adults. C57BL/6 mice of both ages had higher blood cocaine levels than did the corresponding CD-1 mice. Concomitant with lower cocaine levels, periadolescent CD-1 mice had higher blood BZE levels than the adults, suggesting that periadolescents may metabolize cocaine faster. Brain cocaine levels in P42 C57BL/6 mice were similar to those of adults. Cocaine-induced activity did not differ between periadolescent and adult CD-1 mice after a single injection of cocaine, whereas periadolescent C57BL/6 mice had lower activity levels than did the adults after a single cocaine injection. Periadolescent CD-1 mice exhibited higher levels of locomotor activity following cocaine injection than did periadolescent C57BL/6 mice. Following chronic cocaine administration, cocaine and BZE levels in the brains of periadolescent and adult mice did not differ from each other in either strain. However, brain cocaine levels at both ages were lower in CD-1 mice than in C57BL/6 mice. In conclusion, the age and the strain of mouse significantly affect the levels of cocaine obtained in brain and blood following acute administration. Our data are consistent with the notion that CD-1 and C57BL/6 mice metabolize cocaine faster during the early periadolescent period than as adults. Furthermore, potentially important strain differences between CD-1 and C57BL/6 mice were noted in cocaine levels following acute and chronic cocaine administration, and in locomotor activity following acute cocaine administration.
AB - Few studies have examined the influence of the age and the strain of mouse on the pharmacokinetics of psychostimulants, or the role of pharmacokinetics in age-related differences in drug responses. The present study compared concentrations of cocaine, and its metabolite, benzoylecgonine (BZE), in the blood and brain of early (P35) and later (P42) periadolescent and adult (P63) CD-1 and C57BL/6 male mice 15 min after acute intraperitoneal injection of cocaine (20 mg/kg). Brain levels of cocaine and BZE after seven daily cocaine injections in CD-1 and C57BL/6 mice beginning on P35 and on P63 were also measured. P35 periadolescents of both strains had lower blood cocaine levels than did the adults, but only C57BL/6 periadolescents had lower brain cocaine levels than the adults. C57BL/6 mice of both ages had higher blood cocaine levels than did the corresponding CD-1 mice. Concomitant with lower cocaine levels, periadolescent CD-1 mice had higher blood BZE levels than the adults, suggesting that periadolescents may metabolize cocaine faster. Brain cocaine levels in P42 C57BL/6 mice were similar to those of adults. Cocaine-induced activity did not differ between periadolescent and adult CD-1 mice after a single injection of cocaine, whereas periadolescent C57BL/6 mice had lower activity levels than did the adults after a single cocaine injection. Periadolescent CD-1 mice exhibited higher levels of locomotor activity following cocaine injection than did periadolescent C57BL/6 mice. Following chronic cocaine administration, cocaine and BZE levels in the brains of periadolescent and adult mice did not differ from each other in either strain. However, brain cocaine levels at both ages were lower in CD-1 mice than in C57BL/6 mice. In conclusion, the age and the strain of mouse significantly affect the levels of cocaine obtained in brain and blood following acute administration. Our data are consistent with the notion that CD-1 and C57BL/6 mice metabolize cocaine faster during the early periadolescent period than as adults. Furthermore, potentially important strain differences between CD-1 and C57BL/6 mice were noted in cocaine levels following acute and chronic cocaine administration, and in locomotor activity following acute cocaine administration.
KW - Cocaine
KW - Locomotor activity
KW - Periadolescent
KW - Pharmacokinetics
KW - Psychostimulant
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U2 - 10.1016/j.ntt.2004.07.004
DO - 10.1016/j.ntt.2004.07.004
M3 - Article
C2 - 15451047
AN - SCOPUS:4644219664
SN - 0892-0362
VL - 26
SP - 839
EP - 848
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
IS - 6 SPEC. ISS.
ER -