Journal article
Effects of the histamine H₁ receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward
European journal of pharmacology, v 683(1-3), pp 161-165
15 May 2012
PMID: 22445882
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- Effects of the histamine H₁ receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward
- Creators
- Erik B Oleson - Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina, USAMark J FerrisRodrigo A EspañaJill HarpSara R Jones
- Publication Details
- European journal of pharmacology, v 683(1-3), pp 161-165
- Publisher
- Elsevier; Netherlands
- Grant note
- R01 DA021325-05 / NIDA NIH HHS K01DA025279 / NIDA NIH HHS K01 DA025279 / NIDA NIH HHS T32DA007246 / NIDA NIH HHS P20 MD000232 / NIMHD NIH HHS P20 MD000232-03 / NIMHD NIH HHS T32 DA007246 / NIDA NIH HHS K01 DA025279-06 / NIDA NIH HHS R01DA021325 / NIDA NIH HHS R01 DA021325 / NIDA NIH HHS R01 DA030161 / NIDA NIH HHS T32 DA007246-19 / NIDA NIH HHS R01 DA030161-03 / NIDA NIH HHS DA030161 / NIDA NIH HHS MD00232 / NIMHD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000303436200021
- Scopus ID
- 2-s2.0-84860494025
- Other Identifier
- 991014877698904721
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- Web of Science research areas
- Pharmacology & Pharmacy