title: Systemic administration of D-penicillamine prevents the locomotor activation after intra-VTA ethanol administration in rats.
abstract: Although recently published studies seem to confirm the important role displayed by acetaldehyde (ACH), the main metabolite of ethanol, in the behavioral effects of ethanol, the origin of ACH is still a matter of debate. While some authors confer more importance to the central (brain metabolism) origin of ACH, others indicate that the hepatic origin could be more relevant. In this study we have addressed this topic using an experimental approach that combines local microinjections of ethanol into the ventral tegmental area (VTA) (which guarantees the brain origin of the ACH) to induce motor activation in rats together with systemic administration (i.p.) of several doses (0, 12.5, 25 and 50 mg/kg) of D-penicillamine (DP), a sequestering agent of ACH with contrasted efficiency to abolish the behavioral effects of the drug. Our results clearly show that DP prevented in a dose-dependent manner the motor activation induced by intra-VTA ethanol, being the 50 mg/kg dose the most efficient. DP per se did not affect the basal activity of the rats. In order to determine the specificity of the DP action, we also studied the effects of DP 50 mg/kg on the DAMGO-induced motor activation after the intra-VTA administration of this mu-opioid receptors agonist. DP did not significantly modify the motor activation induced by DAMGO thus confirming the specificity of the DP effects. Our results clearly suggest that the brain-derived ACH is necessary to manifest the activating effects resulting from ethanol administration.
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Universitat de València, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Martí-Prats
authors.forename: María José
authors.initials: MJ
authors.lastname: Sánchez-Catalán
authors.forename: Lucía
authors.initials: L
authors.lastname: Hipólito
authors.forename: Alejandro
authors.initials: A
authors.lastname: Orrico
authors.forename: Teodoro
authors.initials: T
authors.lastname: Zornoza
authors.forename: Ana
authors.initials: A
authors.lastname: Polache
authors.forename: Luis
authors.initials: L
authors.lastname: Granero
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D000431:Ethanol / Q000037:antagonists & inhibitors*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010396:Penicillamine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D010396:Penicillamine