Reference : Modulatory function of the H3 histaminergic receptor system in addiction: an example wit...
Scientific congresses and symposiums : Poster
Social & behavioral sciences, psychology : Neurosciences & behavior
Modulatory function of the H3 histaminergic receptor system in addiction: an example with cocaine and ethanol
Brabant, Christian[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
Didone, Vincent[Université de Liège - ULg > Département des sciences cognitives > Psychologie quantitative >]
Tirelli, Ezio[Université de Liège - ULg > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér. >]
Quertemont, Etienne[Université de Liège - ULg > Département des sciences cognitives > Psychologie quantitative >]
Annual forum of the Belgian College of Neuropsychopharmacology and Biological Psychiatry
Belgian College of Neuropsychopharmacology and Biological Psychiatry (BCNBP)
[en] Histamine ; H3 receptors ; Ethanol ; Cocaine
[en] The histaminergic neurotransmission is involved in many biological functions, including the modulation of arousal, fluid balance, food intake, reinforcement and learning. Recently, the results of several studies have also suggested that the central histaminergic system, and particularly the H3 receptors, plays a role in drug addiction. For example, in animal experiments, the administration of H3 agonists and antagonists modulate the self-administration of various drugs including cocaine, amphetamine and alcohol. In the present studies, we used the locomotor stimulant effects of drugs as an index of their abuse potential (most of addictive drugs stimulate locomotor activity, at least at some doses, and this effect is often considered as an intrinsic feature of drug addiction). In two independent experiments, we tested the effects of thioperamide, a histamine H3 antagonist/inverse agonist, on the locomotor stimulant effects of cocaine and ethanol. Our results show that thioperamide modulates the locomotor stimulant effects of both cocaine and ethanol. However, this modulatory effect was surprisingly opposite in direction depending upon the tested drug. Whereas thioperamide potentiated the locomotor stimulant effect of cocaine, it prevented the hyperactivity induced by 2 g/kg ethanol in mice. In the brain, H3 receptors is both a histamine autoreceptor modulating the synaptic release of histamine and a heteroreceptor that modulates the release of other neurotransmitters such as dopamine, acetylcholine and GABA. It is therefore likely that the modulatory action of thioperamide on cocaine and ethanol stimulant effects involves different neurotransmitter system. This conclusion is supported by our preliminary results on knock-out mice genetically devoid of histamine. In such knock-out mice, ethanol retains its stimulant properties, suggesting that histamine release is not involved in this effect. In contrast, these knock-out mice showed a reduced cocaine-induced hyperactivity, indicating that histamine release play a significant role in the stimulant effect of cocaine.
Centre de Neurosciences Cognitives et Comportementales