A new brain area affected by 3,4-methylenedioxymethamphetamine: A microdialysis-biotelemetry study.
The widespread abuse of 3,4-methylenedioxymethamphetamine (MDMA) has intensified the need to learn more about this drug (e.g. its effects, its mechanism of action, brain areas affected). MDMA-induced hyperthermia is a severe physiological event not only because it can produce severe adverse consequences in human as well as experimental animals, but also because it plays a major role in determining the severity of the long-term MDMA-induced neurotoxicity that occurs. However, the effects of MDMA on the preoptic anterior hypothalamus, the main brain area responsible for control of body temperature, are still unknown. In vivo microdialysis-biotelemetry and pharmacological testing were used to determine whether the preoptic anterior hypothalamus is among the brain areas affected by MDMA by investigating the role of the dopamine neurotransmitter system. We examined the effect of a hyperthermic dose of MDMA on the extracellular level of dopamine in the preoptic anterior hypothalamus, and whether this effect is related to the acute hyperthermic response. The administration of a hyperthermic dose of MDMA (20 mg/kg) is accompanied by an increase in the extracellular level of dopamine in the preoptic anterior hypothalamus. Both the hyperthermia and augmented level of dopamine in the preoptic anterior hypothalamus after intraperitoneal injection of MDMA were significantly reduced by the pretreatment with D(1)-selective dopamine receptor antagonist, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzapine (SCH 23390). These data provide the first in vivo evidence that the effects of MDMA extend to preoptic anterior hypothalamus.
Benamar
Khalid
K
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. kbenamar@temple.edu
Geller
Ellen B
EB
Adler
Martin W
MW
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013686:Telemetry
D002491:Central Nervous System Agents; D017447:Receptors, Dopamine D1; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine