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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 358, Issue 4, pp 423–429 | Cite as

Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade

  • Hans C. Dringenberg
  • M. Angelica de Souza-Silva
  • Rainer K. W. Schwarting
  • Joseph P. Huston
Original article

Abstract

The dopaminergic system plays a central role in the processing of reward or reinforcement since drugs that have reinforcing properties all share the ability to elevate dopamine (DA) levels in the nucleus accumbens or neostriatum. Histamine H1 receptor antagonists are known to have reinforcing effects in humans and laboratory rats. Here, we examined the effect of systemic (i.p.) treatment with two H1 antagonists, chlorpheniramine and pyrilamine, on the extracellular levels of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the neostriatum and nucleus accumbens of urethane-anesthetized rats. Dopamine and metabolites were measured using in vivo microdialysis and HPLC with electrochemical detection. Saline injections did not produce significant effects on DA, DOPAC, or HVA levels in the neostriatum or nucleus accumbens. In the neostriatum, chlorpheniramine administration (5 and 20 mg/kg) produced a sustained increase in DA to approximately 140 and 180% of pre-injection baseline levels, respectively. In the nucleus accumbens, chlorpheniramine (20 mg/kg) produced a transient increase in DA levels to about 300% of baseline. In both the neostriatum and nucleus accumbens, DOPAC and HVA decreased after chlorpheniramine treatment. Pyrilamine administration (10 and 20 mg/kg) produced a sustained increase in neostriatal DA levels to 140 and 165%, respectively, and accumbens DA increased transiently to 230% after a dose of 20 mg/kg. Levels of neostriatal and accumbens DOPAC and HVA decreased after pyrilamine treatment. These results show that H1 antagonists can potently enhance DA levels in the neostriatum and nucleus accumbens of urethane-anesthetized rats. The neurochemical effects on DA and its metabolites seen here (increased DA, decreased DOPAC and HVA) are similar to those commonly observed with drugs of abuse (e.g. psychostimulants). The interaction of H1 antagonists with dopaminergic transmission may explain the reinforcing effects and abuse potential associated with these compounds.

Key words Dopamine Histamine H1 receptor antagonists Neostriatum Nucleus accumbens Microdialysis 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Hans C. Dringenberg
    • 2
  • M. Angelica de Souza-Silva
    • 1
  • Rainer K. W. Schwarting
    • 1
  • Joseph P. Huston
    • 1
  1. 1.Institute of Physiological Psychology I and Center for Biological and Medical Research, Heinrich Heine University of Düsseldorf, D-40225 Düsseldorf, GermanyDE
  2. 2.Department of Psychology, Queen’s University, Kingston, Ontario, CanadaCA

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