title: A role for D1 dopamine receptors in striatal methamphetamine-induced neurotoxicity.
abstract: Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia.
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, 401 MREB, 20 North 1900 East, Salt Lake City, UT 84112, United States. Electronic address: da.friend@utah.edu.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Friend
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Keefe
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D005334:Fever / Q000139:chemically induced; D006358:Hot Temperature; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D008694:Methamphetamine; D004298:Dopamine
keywords: DA; Dopamine; Dopamine receptor; METH; Methamphetamine; Neurotoxicity; PND; dopamine; methamphetamine; post-natal day