Psychomotor stimulant drugs of abuse cause brain damage that is dependent on elevated body temperature. This year, we continued to examine brain and body temperature changes during exposure to two active components of bath salts (MDPV, Methylone) a new class of addictive drugs. We also comparing the effects of these drugs with those induced by other structurally similar analogs, particularly MDMA. We found that MDMA at relatively low dose induces modest brain and body hyperthermia, which is greatly potentiated when the drug is administered during social interaction and at moderately warm ambient temperature. We also established a critical role of centrally-mediated cutaneous vasoconstriction as a primary mechanism determining hyperthermic effects of MDMA. While MDPV and methylone also induced comparable hyperthermic effects and motor activation, these effects were less dependent upon activity state and environmental conditions. We also tested different pharmacological strategies to reverse MDMA-induced brain and body hyperthermia and found that centrally-acting clozapine is more effective to reverse hyperthermia than alpha-beta adrenocentor blockers that directly dilate blood vessels.

Project Start
Project End
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Budget End
Support Year
15
Fiscal Year
2015
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
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Solis Jr, Ernesto; Bola, R Aaron; Fasulo, Bradley J et al. (2017) Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation. ACS Chem Neurosci 8:265-271
Solis, Ernesto; Cameron-Burr, Keaton T; Shaham, Yavin et al. (2017) Fentanyl-Induced Brain Hypoxia Triggers Brain Hyperglycemia and Biphasic Changes in Brain Temperature. Neuropsychopharmacology :
Kiyatkin, Eugene A; Ren, Suelynn E (2017) MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment. Curr Top Behav Neurosci 32:183-207
Bola, R Aaron; Kiyatkin, Eugene A (2016) Robust Brain Hyperglycemia during General Anesthesia: Relationships with Metabolic Brain Inhibition and Vasodilation. Front Physiol 7:39
Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T et al. (2016) Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction. Neuropsychopharmacology 41:549-59
Kiyatkin, Eugene A; Sharma, Hari S (2016) Breakdown of Blood-Brain and Blood-Spinal Cord Barriers During Acute Methamphetamine Intoxication: Role of Brain Temperature. CNS Neurol Disord Drug Targets 15:1129-1138
Sharma, Hari Shanker; Kiyatkin, Eugene A; Patnaik, Ranjana et al. (2015) Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/51. Mol Neurobiol 52:1023-33
Kiyatkin, Eugene A; Kim, Albert H; Wakabayashi, Ken T et al. (2015) Effects of social interaction and warm ambient temperature on brain hyperthermia induced by the designer drugs methylone and MDPV. Neuropsychopharmacology 40:436-45
Carvalho, FĂ©lix; Kiyatkin, Eugene A; Rusyniak, Daniel E et al. (2015) Temperature in the spotlight of drug abuse research. Temperature (Austin) 2:27-8
Kiyatkin, Eugene A; Sharma, Hari S (2015) Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells. CNS Neurol Disord Drug Targets 14:282-94

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