Mechanism of an exaggerated locomotor response to a low-dose challenge of methamphetamine.
Previous studies using phenylethylamine psychostimulants such as amphetamine (AMPH) have demonstrated that pretreatment with a high-dose of drug followed by a low-dose challenge injection (3 h later) results in an exaggerated behavioral response. In order to explore the mechanism of this exaggerated or what has been suggested to be a "sensitized" response, we investigated the effects of methamphetamine (METH) in a similar treatment paradigm. The current study found that, as suggested by previous studies, a low-dose challenge with METH substantially increased the locomotor response in animals that received a high-dose pretreatment (3.5 h prior to challenge). We also observed that rats displayed an increase in the concentrations of METH and its metabolite AMPH in the striatum following the low-dose challenge of METH if they were pretreated with METH versus saline. A similar pattern for METH and AMPH levels was measured in the plasma. Taken together, these results suggest that the accumulation of drug in animals pretreated with high-dose METH contributes to the overall enhanced behavioral response following challenges with low-doses of METH.
Frankel
Paul S
PS
University of Utah, Department of Pharmacology and Toxicology, Salt Lake City, UT 84112, USA. paul.frankel@pharm.utah.edu
Hoonakker
Amanda J
AJ
Danaceau
Jonathan P
JP
Hanson
Glen R
GR
D000661:Amphetamine / Q000097:blood / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine