Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice

NEUROPHARMACOLOGY

卷:134

Article

Gannon, Brenda M.¹  Williamson, Adrian²  Rice, Kenner C.^3,4  Fantegrossi, William E.¹ 

[1] Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA

[2] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA

[3] NIDA, Mol Targets & Med Discovery Branch, Bethesda, MD 20852 USA

[4] NIAAA, Bethesda, MD 20852 USA

关键词: MDPV;    Monoamines;    Bath salts;    Locomotor activity;    Temperature;   

DOI  :  10.1016/j.neuropharm.2017.09.004

来源: Elsevier

【 摘 要 】

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit bath salts products, and in vitro studies implicate monoamine transporters as mediators of its pharmacological effects. Locomotor and thermoregulatory effects of MDPV depend on ambient temperature, so the current studies aimed to gauge the involvement of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in MDPV-induced locomotor stimulation and hyperthermia in the mouse at different ambient temperatures. Mice were pretreated with the selective 5-HT-reuptake inhibitor fluoxetine (3 mg/kg), the NE-reuptake inhibitor desipramine (3 mg/kg), the DA-reuptake inhibitor bupropion (10 mg/kg), or saline, followed by 10 mg/kg MDPV while thermoregulation and locomotor activity were monitored via radiotelemetry. In other studies, mice were pretreated for three days with saline, 100 mg/kg of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA), or 100 mg/kg of the tyrosine hydroxylase inhibitor a-methylpara-tyrosine (a-MPT) before receiving 10 mg/kg MDPV on the fourth day. All manipulations were conducted at both 20 degrees C and 28 degrees C ambient temperatures. MDPV increased locomotor activity under both ambient conditions and modestly increased core body temperature at 20 degrees C; however, neither pretreatment with monoamine reuptake inhibitors nor monoamine synthesis inhibitors significantly altered these effects. At 28 degrees C, MDPV induced a more pronounced hyperthermic effect which was attenuated by bupropion, desipramine, or fluoxetine pretreatment, but not by the monoamine synthesis inhibitors These results suggest that MDPV may have a more complex pharmacological profile than suggested by in vitro studies, perhaps extending beyond interactions with monoamine transporters. A more thorough binding profile of MDPV at various brain recognition sites should be developed. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

【 授权许可】

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