Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats.
Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.
Clark
Robert E
RE
Veterans Affairs Medical Center, San Diego, California, USA. reclark@ucsd.edu
Kuczenski
Ronald
R
Segal
David S
DS
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D004298:Dopamine