The pharmacokinetic properties of methamphetamine in rats with previous repeated exposure to methamphetamine: the differences between Long-Evans and Wistar rats.
Repeated treatment with methamphetamine (METH) causes long-term behavioral changes, so-called behavioral sensitization (BS), in humans as well as experimental animals. However, there are no reports as to whether repeated METH treatment can establish BS in stress-sensitive Long-Evans (LE) rats. Thus, we investigated the effect of repeated METH treatment (5 mg/kg x 5 days) on the establishment of BS in LE rats. Wistar (WIS) rats were used as a reference. In LE rats, repeated METH treatment failed to cause BS although it did enhance METH-induced hyperlocomotion in WIS rats. The levels of METH in brain dialysate and the ratio of the area under the concentration-time curve area in plasma to that in brain dialysate was increased in repeated METH-treated WIS rats as reported previously, but not in repeated METH-treated LE rats. METH increases plasma corticosterone (CORT) in both strains. However, the intensity of increment of CORT by repeated METH was lower in LE rats than that in WIS rats. Repeated METH treatment decreased the expression of METH-transposable and CORT-sensitive transporter, organic cation transporter 3 (OCT3), in the brain of WIS rats. However, the intensity of the decrement of OCT3 with repeated METH treatment was similar between both strains. Taken together, these results suggest that the lack of establishment of BS in LE rats might have been caused by the unchanged brain penetration of METH after repeated METH administration, and that the differential CORT response to METH is an important strain difference.
Fujimoto
Yohei
Y
Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan.
Kitaichi
Kiyoyuki
K
Nakayama
Hironao
H
Ito
Yukiko
Y
Takagi
Kenji
K
Takagi
Kenzo
K
Hasegawa
Takaaki
T
D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects*; D001711:Biotransformation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics*; D003345:Corticosterone / Q000097:blood; D007279:Injections, Subcutaneous; D008297:Male; D008694:Methamphetamine / Q000097:blood / Q000493:pharmacokinetics*; D009043:Motor Activity / Q000187:drug effects; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013045:Species Specificity; D019966:Substance-Related Disorders / Q000378:metabolism*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D008694:Methamphetamine; D003345:Corticosterone