Biomaterial Database

Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, and para-methoxyamphetamine-induced hyperthermia. 2007

Emily Joy Jaehne, and Abdallah Salem, and Rodney James Irvine

Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Level 5 Medical School North, Adelaide, South Australia 5005, Australia. emily.jaehne@adelaide.edu.au

BACKGROUND Cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), and para-methoxyamphetamine (PMA) disrupt normal thermoregulation in humans, with PMA being associated with more severe cases of hyperthermia. Harm minimization advice on how to prevent overheating depends on appropriate thermoregulatory behavior by drug users. OBJECTIVE The purpose of the current study was to establish dose-response relationships for the effects of a number of commonly used illicit stimulants and investigate the behavioral response to increased core temperature. METHODS Sprague-Dawley rats with telemetry implants were administered either saline or 4, 12, 26, 40 or 80 micromol/kg of cocaine, methamphetamine, MDMA, or PMA and confined to an ambient temperature of 30 degrees C for 30 min, before being able to choose their preferred temperature on a thermally graded runway (11-41 degrees C). RESULTS The increased core temperature caused by administration of cocaine, methamphetamine, and MDMA treatment led to the animals seeking the cool end of the runway to correct their core temperature, although this did not occur in PMA-treated rats. The order of potency for increasing core temperature was methamphetamine >PMA = MDMA>cocaine. This differed to the slopes of the dose-response curves where MDMA and PMA showed the steepest slope for the doses used followed by methamphetamine then cocaine. CONCLUSIONS These results suggest that behavioral aspects of thermoregulation are important in assessing the potential of individual drugs to cause harmful increases in core temperature.

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008297	Male		Males
D008694	Methamphetamine	A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.	Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D001833	Body Temperature Regulation	The processes of heating and cooling that an organism uses to control its temperature.	Heat Loss,Thermoregulation,Regulation, Body Temperature,Temperature Regulation, Body,Body Temperature Regulations,Heat Losses,Loss, Heat,Losses, Heat,Regulations, Body Temperature,Temperature Regulations, Body,Thermoregulations
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003042	Cocaine	An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.	Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005334	Fever	An abnormal elevation of body temperature, usually as a result of a pathologic process.	Pyrexia,Fevers,Pyrexias
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man