title: Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice.
abstract: Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway.
authors.affiliation: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Univ Estadual Paulista-UNESP, Araraquara, SP, Brazil; Joint Graduate Program in Physiological Sciences, UFSCar/UNESP, São Carlos/Araraquara, SP, Brazil; Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil.
authors.forename: Gessynger
authors.initials: G
authors.lastname: Morais-Silva
authors.affiliation: Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: Ferreira-Santos
authors.affiliation: Laboratory of Pharmacology, School of Pharmaceutical Sciences, Univ Estadual Paulista-UNESP, Araraquara, SP, Brazil; Joint Graduate Program in Physiological Sciences, UFSCar/UNESP, São Carlos/Araraquara, SP, Brazil. Electronic address: marcelo@fcfar.unesp.br.
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Marin
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D002492:Central Nervous System Depressants; D054828:Histamine H3 Antagonists; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; C007111:conessine; D006719:Homovanillic Acid
keywords: Alcohol addiction; Conditioned place preference; Conessine; H(3) receptor antagonist; Monoamines; Psychostimulation