title: Mephedrone alters basal ganglia and limbic neurotensin systems.
abstract: Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: German
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Hoonakker
authors.forename: Annette E
authors.initials: AE
authors.lastname: Fleckenstein
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology; D003627:Data Interpretation, Statistical; D015198:Designer Drugs / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D009496:Neurotensin / Q000031:analogs & derivatives / Q000187:drug effects* / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D018028:Receptors, Neurotensin / Q000819:agonists / Q000378:metabolism; D012646:Self Administration; D013373:Substance P / Q000378:metabolism / Q000502:physiology
chemical_list: D015198:Designer Drugs; C117269:PD 149163; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018028:Receptors, Neurotensin; D013373:Substance P; D009496:Neurotensin; D008694:Methamphetamine; C548233:mephedrone
keywords: basal Ganglia; dopamine; limbic System; mephedrone; neurotensin; stimulants