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Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Oct; 358(4):423-9.NS

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.

Authors+Show Affiliations

Department of Psychology, Queen's University, Kingston, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9826064

Citation

Dringenberg, H C., et al. "Increased Levels of Extracellular Dopamine in Neostriatum and Nucleus Accumbens After Histamine H1 Receptor Blockade." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 358, no. 4, 1998, pp. 423-9.
Dringenberg HC, de Souza-Silva MA, Schwarting RK, et al. Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1998;358(4):423-9.
Dringenberg, H. C., de Souza-Silva, M. A., Schwarting, R. K., & Huston, J. P. (1998). Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade. Naunyn-Schmiedeberg's Archives of Pharmacology, 358(4), 423-9.
Dringenberg HC, et al. Increased Levels of Extracellular Dopamine in Neostriatum and Nucleus Accumbens After Histamine H1 Receptor Blockade. Naunyn Schmiedebergs Arch Pharmacol. 1998;358(4):423-9. PubMed PMID: 9826064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade. AU - Dringenberg,H C, AU - de Souza-Silva,M A, AU - Schwarting,R K, AU - Huston,J P, PY - 1998/11/24/pubmed PY - 1998/11/24/medline PY - 1998/11/24/entrez SP - 423 EP - 9 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 358 IS - 4 N2 - 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. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/9826064/Increased_levels_of_extracellular_dopamine_in_neostriatum_and_nucleus_accumbens_after_histamine_H1_receptor_blockade_ L2 - https://dx.doi.org/10.1007/pl00005274 DB - PRIME DP - Unbound Medicine ER -