Abstract

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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Publisher Full Text

Authors

Oleson EB, Ferris MJ, España RA, Harp J, Jones SR

Institution

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA.

Source

European journal of pharmacology 683:1-3 2012 May 15 pg 161-5

MeSH

Animals
Behavior, Animal
Benztropine
Central Nervous System Stimulants
Cocaine
Cocaine-Related Disorders
Dopamine Uptake Inhibitors
Exploratory Behavior
Histamine H1 Antagonists
Kinetics
Male
Mice
Mice, Inbred C57BL
Motor Activity
Nucleus Accumbens
Piperidines
Psychomotor Agitation
Reward
Spatial Behavior
Street Drugs

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22445882