title: Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine.
abstract: Methamphetamine (Meth) is a widely abused psychostimulant that causes long-term dopamine (DA) and serotonin (5-HT) depletions. Stress and Meth abuse are comorbid events in society and stress exacerbates Meth-induced monoaminergic terminal damage. Stress is also known to produce neuroinflammation. This study examined the role of the neuroinflammatory mediator, cyclooxygenase (COX), in the depletions of monoamines caused by serial exposure to chronic unpredictable stress (CUS) and Meth. CUS produced an increase in COX-2 protein expression and enhanced Meth-induced monoaminergic depletions in the striatum and hippocampus. The enhanced DA and 5-HT depletions in the striatum, but not the hippocampus, were prevented by pretreatment with COX inhibitor, ketoprofen, during stress or during Meth; however, ketoprofen did not attenuate the monoaminergic damage caused by Meth alone. The COX-dependent enhancement by stress of Meth-induced monoaminergic depletions was independent of hyperthermia, as ketoprofen did not attenuate Meth-induced hyperthermia. In addition, the EP1 receptor antagonist, SC-51089, did not attenuate DA or 5-HT depletions caused by stress and Meth. These findings illustrate that COX activity, but not activation of the EP1 receptor, is responsible for the potentiation of Meth-induced damage to striatal monoamine terminals by stress and suggests the use of anti-inflammatory drugs for mitigating the neurotoxic effects associated with the combination of stress and Meth.
authors: University of Toledo, College of Medicine, Department of Neurosciences, 3000 Arlington Avenue, Mail Stop # 1007, Toledo, OH 43614, USA. nicole.fazo@utoledo.edu
authors: Nicole A
authors: NA
authors: Northrop
authors: Bryan K
authors: BK
authors: Yamamoto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010077:Oxazepines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D006834:Hydrazines; D010077:Oxazepines; C086836:SC 51089; D008694:Methamphetamine; D011451:Prostaglandin-Endoperoxide Synthases
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