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The psychostimulant and rewarding effects of cocaine in histidine decarboxylase knockout mice do not support the hypothesis of an inhibitory function of histamine on reward

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Abstract

Rationale and objectives

Lesion studies have shown that the tuberomammillary nucleus (TM) exerts inhibitory effects on the brain reward system. To determine whether histamine from the TM is involved in that reward inhibitory function, we assessed the stimulant and rewarding effects of cocaine in knockout mice lacking histidine decarboxylase (HDC KO mice), the histamine-synthesizing enzyme. If histamine actually plays an inhibitory role in reward, then it would be expected that mice lacking histamine would be more sensitive to the behavioral effects of cocaine.

Materials and methods

The first experiment characterized spontaneous locomotion and cocaine-induced hyperactivity (0, 8, and 16 mg/kg, i.p.) in wild-type and HDC KO mice. The rewarding effects of cocaine were investigated in a second experiment with the place-conditioning technique.

Results

The first experiment demonstrated that histidine decarboxylase mice showed reduced exploratory behaviors but normal habituation to the test chambers. After habituation to the test chambers, HDC KO mice were slightly, but significantly, less stimulated by cocaine than control mice. This finding was replicated in the second experiment, when cocaine-induced activity was monitored with the place-conditioning apparatus. Furthermore, a significant place preference was present in both genotypes for 8 and 16 mg/kg cocaine, but not for 2 and 4 mg/kg.

Conclusions

Our data confirm previous results demonstrating that HDC KO mice show reduced exploratory behaviors. However, contrary to the hypothesis that histamine plays an inhibitory role in reward, histamine-deficient mice were not more responsive to the psychostimulant effects of cocaine.

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Acknowledgements

The present research was supported by the Belgian National Funds for Scientific Research (FNRS), grant F.R.F.C. N°2.4533.02F to Ezio Tirelli.

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Authors and Affiliations

  1. Unité de Recherche en Psychologie Expérimentale et en Neurosciences Cognitives (URPENC), Université de Liège, Boulevard du Rectorat, B-32, 4000, Liège, Belgium

    Christian Brabant, Etienne Quertemont & Ezio Tirelli

  2. INSERM-U628, IFR19, Département de Médecine Expérimentale, Faculté de Médecine, Université Claude Bernard, 69373, Lyon, France

    Christelle Anaclet & Jian-Sheng Lin

  3. Department of Engineering, Tohoku University, School of Medicine, Aoba-ku, Sendai, 980-8775, Japan

    Hiroshi Ohtsu

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  1. Christian Brabant
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  2. Etienne Quertemont
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  3. Christelle Anaclet
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  4. Jian-Sheng Lin
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  5. Hiroshi Ohtsu
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  6. Ezio Tirelli
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Correspondence to Ezio Tirelli.

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Brabant, C., Quertemont, E., Anaclet, C. et al. The psychostimulant and rewarding effects of cocaine in histidine decarboxylase knockout mice do not support the hypothesis of an inhibitory function of histamine on reward. Psychopharmacology 190, 251–263 (2007). https://doi.org/10.1007/s00213-006-0603-0

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  • DOI: https://doi.org/10.1007/s00213-006-0603-0

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