title: Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.
abstract: Administration of methamphetamine (METH) alters limbic-related (LR) neurotensin (NT) systems. Thus, through a D1-receptor mechanism, noncontingent high doses (5-15 mg kg(-1)), and likely self-administration, of METH appears to reduce NT release causing its accumulation and an elevation of NT-like immunoreactivity (NTLI) in limbic-related NT pathways. For comparison, we tested the effect of low doses of METH, that are more like those used in therapy, on NTLI in the core and shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg). METH at the dose of 0.25 mg kg(-1) in particular, but not 1.00 mg kg(-1), decreased NTLI concentration in all of the LR structures studied, except for the prefrontal cortex; however, these effects were rapid and brief being observed at 5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels were reduced after the low dose of METH, the effect was blocked by pretreatment with either a D1 or a D2 antagonist. Thus, opposite to high doses like those associated with abuse, the therapeutic-like low-dose METH treatment induced reduction in NT tissue levels likely reflected an increase in NT release and a short-term depletion of the levels of this neuropeptide in LR structures, manifesting features comparable to the response of basal ganglia NT systems to similar low doses of METH.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Alburges
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hoonakker
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Cordova
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Robson
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McFadden
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Martin
authors.affiliation: School of Dentistry and Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009496:Neurotensin / Q000378:metabolism*; D011863:Radioimmunoassay; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009496:Neurotensin; D008694:Methamphetamine
keywords: basal ganglia; dopamine antagonists; methamphetamine; neurotensin; stimulant