Effects of chronic unpredictable stress and methamphetamine on hippocampal glutamate function.
Although stress and methamphetamine (Meth) can independently and acutely affect glutamate transmission in the hippocampus, no studies have examined how chronic unpredictable stress modulates glutamate function and alters glutamate responsiveness to Meth. Therefore, the effects of chronic unpredictable stress on markers of glutamate function and subsequent Meth-induced increases in extracellular glutamate in the dorsal hippocampus were examined. Ten days of chronic unpredictable stress increased the plasmalemmal glial-glutamate transporter 2 (EAAT2) and increased vesicular glutamate transporter-1 (VGLUT1) immunoreactivity in a vesicle associated fraction. In addition, a 2-fold increase in vesicular glutamate content was observed. Chronic stress also enhanced Meth-induced increases in extracellular glutamate in the dorsal hippocampus in a TTX dependent manner. Overall, the finding that chronic stress resulted in an upregulation of glutamate function and an enhanced glutamate response to Meth may have implications for glutamate responsiveness in chronically stressed animals exposed to other challenges or stressors.
Raudensky
Jamie
J
Boston University School of Medicine, Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics L-613, 715 Albany St., Boston, MA 02118, USA.
Yamamoto
Bryan K
BK
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
D000697:Central Nervous System Stimulants; D027342:Excitatory Amino Acid Transporter 2; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid; D008694:Methamphetamine