title: Synthetic cathinone MDPV downregulates glutamate transporter subtype I (GLT-1) and produces rewarding and locomotor-activating effects that are reduced by a GLT-1 activator.
abstract: Synthetic cathinones produce dysregulation of monoamine systems, but their effects on the glutamate system and the influence of glutamate on behavioral effects related to cathinone abuse are unknown. A principal regulator of glutamate homeostasis is glutamate transporter subtype 1 (GLT-1), an astrocytic protein that clears glutamate from the extracellular space and influences behavioral effects of established psychostimulants. We hypothesized that repeated administration of the synthetic cathinone, MDPV (3,4-methylenedioxypyrovalerone), would affect GLT-1 expression in the corticolimbic circuit, and that a GLT-1 activator (ceftriaxone, CTX) would reduce rewarding and locomotor-stimulant effects of MDPV in rats. GLT-1 protein expression in the nucleus accumbens (NAcc), but not prefrontal cortex (PFC), was decreased following withdrawal (2, 5 and 10 days) from repeated MDPV treatment, but not immediately after the last MDPV injection. CTX (200 mg/kg) pretreatment did not affect acute locomotor activation produced by MDPV (0.5, 1, 3 mg/kg). However, CTX (200 mg/kg) administered during a 7-day MDPV treatment paradigm attenuated the development of MDPV-induced sensitization of repetitive movements in rats challenged with MDPV following 11 days of drug abstinence. Pretreatment with CTX (200 mg/kg) during a 4-day MDPV (2 mg/kg) conditioned place preference (CPP) paradigm reduced the development of place preference produced by MDPV. The present data demonstrate dysregulation of corticolimbic glutamate transport systems during withdrawal from chronic MDPV exposure, and show that a GLT-1 transporter activator disrupts behavioral effects of MDPV that are related to synthetic cathinone abuse.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Gregg
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Callum
authors.initials: C
authors.lastname: Hicks
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Sunil U
authors.initials: SU
authors.lastname: Nayak
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Tallarida
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Nucero
authors.affiliation: Fox Chase Chemical Diversity Center, Doylestown, PA, United States.
authors.forename: Garry R
authors.initials: GR
authors.lastname: Smith
authors.affiliation: Fox Chase Chemical Diversity Center, Doylestown, PA, United States.
authors.forename: Allen B
authors.initials: AB
authors.lastname: Reitz
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States; Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, United States. Electronic address: scott.rawls@temple.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D027342:Excitatory Amino Acid Transporter 2 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D012201:Reward; D000094982:Synthetic Cathinone
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D027342:Excitatory Amino Acid Transporter 2; D011759:Pyrrolidines; C493395:Slc1a2 protein, rat; C023665:cathinone; D002443:Ceftriaxone; D000094982:Synthetic Cathinone
keywords: Bath salts; Behavioral sensitization; Cathinone; Ceftriaxone; Conditioned place preference; GLT-1; Glutamate; MDPV