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Effects of the histamine H₁ receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward
Journal article   Open access   Peer reviewed

Effects of the histamine H₁ receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward

Erik B Oleson, Mark J Ferris, Rodrigo A España, Jill Harp and Sara R Jones
European journal of pharmacology, v 683(1-3), pp 161-165
15 May 2012
DOI: https://doi.org/10.1016/j.ejphar.2012.03.003
PMID: 22445882
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.ejphar.2012.03.003View
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Abstract

Central Nervous System Stimulants - pharmacology Dopamine Uptake Inhibitors - therapeutic use Motor Activity - drug effects Male Cocaine-Related Disorders - physiopathology Central Nervous System Stimulants - agonists Cocaine - agonists Psychomotor Agitation - etiology Central Nervous System Stimulants - therapeutic use Piperidines - pharmacology Histamine H1 Antagonists - pharmacology Benztropine - analogs & derivatives Exploratory Behavior - drug effects Behavior, Animal - drug effects Spatial Behavior - drug effects Dopamine Uptake Inhibitors - pharmacology Mice, Inbred C57BL Central Nervous System Stimulants - toxicity Cocaine - pharmacology Animals Histamine H1 Antagonists - therapeutic use Cocaine - toxicity Piperidines - therapeutic use Cocaine-Related Disorders - drug therapy Mice Street Drugs - toxicity Kinetics Reward Nucleus Accumbens - drug effects Street Drugs - pharmacology
Diphenylpyraline hydrochloride (DPP) is an internationally available antihistamine that produces therapeutic antiallergic effects by binding to histamine H₁ receptors. The complete neuropharmacological and behavioral profile of DPP, however, remains uncharacterized. Here we describe studies that suggest DPP may fit the profile of a potential agonist replacement medication for cocaine addiction. Aside from producing the desired histamine reducing effects, many antihistamines can also elicit psychomotor activation and reward, both of which are associated with increased dopamine concentrations in the nucleus accumbens (NAc). The primary aim of this study was to investigate the potential ability of DPP to inhibit the dopamine transporter, thereby leading to elevated dopamine concentrations in the NAc in a manner similar to cocaine and other psychostimulants. The psychomotor activating and rewarding effects of DPP were also investigated. For comparative purposes cocaine, a known dopamine transporter inhibitor, psychostimulant and drug of abuse, was used as a positive control. As predicted, both cocaine (15 mg/kg) and an equimolar dose of DPP (14 mg/kg) significantly inhibited dopamine uptake in the NAc in vivo and produced locomotor activation, although the time-course of pharmacological effects of the two drugs was different. In comparison to cocaine, DPP showed a prolonged effect on dopamine uptake and locomotion. Furthermore, cocaine, but not DPP, produced significant conditioned place preference, a measure of drug reward. The finding that DPP functions as a potent dopamine uptake inhibitor without producing significant rewarding effects suggests that DPP merits further study as a potential candidate as an agonist pharmacotherapy for cocaine addiction.

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Web of Science research areas
Pharmacology & Pharmacy
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