Methamphetamine-induced neural and cognitive changes in rodents.
OBJECTIVE
Although psychostimulant drug abuse carries with it several potential health risks, the chronic abuse of amphetamines carries the danger of permanent brain injury. The purpose of these experiments is to develop animal models to understand the long-lasting influences of methamphetamine exposure on cerebral cortex and cognitive function.


METHODS
The approach taken is to administer a regimen of methamphetamine known to be neurotoxic to dopamine and serotonin nerve terminals in the rat, and to investigate the influences of that dosing regimen on (i) cortical neuron integrity and function using anatomical stains and (ii) novel object recognition memory.


RESULTS
In rodents, repeated administration of methamphetamine during a single day produces long-lasting damage to striatal dopamine and forebrain serotonin terminals as well as degeneration of somatosensory cortical neurons. The degeneration of somatosensory cortical neurons may represent only the most visible form of long-term deleterious effects on cerebral cortex, as exposure of rats to methamphetamine can reduce the immediate early gene responses of neurons in widespread cortical areas, even long after exposure to the drug. Together with the death and long-lasting functional impairments of cortical neurons, rats exposed to methamphetamine have impaired cognitive function. When tested for object recognition memory, methamphetamine-treated rats show deficiencies lasting for at least 3 weeks after drug exposure.


CONCLUSIONS
Using a rodent model, these findings provide an avenue to study the cortical influences of methamphetamine and their cognitive sequelae.
Marshall
John F
JF
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA. jfmarsha@uci.edu
Belcher
Annabelle M
AM
Feinstein
Erin M
EM
O'Dell
Steven J
SJ
D019969:Amphetamine-Related Disorders / Q000150:complications*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D003344:Cortical Synchronization / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine