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 in relation to the permeability of brain-blood barrier during exposure to meth-amphetamine. We also examined how permeability of the blood-brain temperature depends on brain temperature. We found that meth-amphetamine induces the leakage of brain-blood barrier and the degree of this leakage depends on drug-induced increase of brain temperature. This year, in collaboration with Dr. Sharma (Uppsala University, Sweden), we examined acute morphological changes in brain cells during acute methamphetamine intoxication and passive brain heating. We also continued thermorecording studis, in which we examined motivated feeding and drinking behavior established by high-sugar-containing liquids. The latter work is in preparation for publication. We also continued our studies of the central mechanisms underlying addictive properties of cocaine and its physiological effects. Particularly, we examined neuronal effects of iv cocaine with those induced by cocaine methiodide, a cocaine s derivative that fails to cross blood-brain barrier. We found that both drugs have similar excitatory effects of central neurons, implicating peripheral K+ and Na+ channels as an important substrate involved in mediating the acute stimulatory effects of iv cocaine. Our thermorecording work was supplemented by parallel electrophysiological studies, using single-unit recording with iontophoresis in awake rats. This approach appears to be an important tool for the study of central mechanisms of action of various drugs of abuse and drug-taking behavior. It provides novel information to examine the role of environmental factors in adverse health effects of addictive drug use.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2009
Total Cost
$1,061,074
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
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
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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