title: Activity and expression of enkephalinase and aminopeptidase N in regions of the mesocorticolimbic system are selectively modified by acute ethanol administration.
abstract: Opioid peptides play a key role in ethanol reinforcement and alcohol drinking behavior. However, regulation of opioid levels by peptidase-degrading activities in ethanol's actions in brain is still unclear. The aim of this work was to study the acute effects of ethanol (2.5 g/kg) on enkephalinase (NEP) and aminopeptidase N (APN) activities and expression in regions of the mesocorticolimbic system, as well as on corticosterone levels in serum for up to 24 h after administration. Enzymatic activities were measured by fluorometric assays, mRNA's expression by reverse transcriptase polymerase chain reaction (RT-PCR) and corticosterone levels by radioimmunoassay. Acute ethanol administration modified peptidase activity and expression with different kinetics. Ethanol induced a transitory increase and decrease in NEP and APN activities in the frontal cortex (FC) and ventral tegmental area (VTA), whereas only increases in these activities were observed in the nucleus accumbens (NAcc). Ethanol induced an increase in NEP mRNA in the FC and decreases in APN mRNA in the FC and NAcc. In contrast, ethanol produced biphasic effects on both enzymes expression in the VTA. Corticosterone levels were not changed by ethanol. Our results suggest that NEP and APN could play a main role in ethanol reinforcement through regulation of opioid levels in mesolimbic areas.
authors.affiliation: Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370, México, DF, Mexico.
authors.forename: Marcela
authors.initials: M
authors.lastname: Morales-Mulia
authors.forename: Patricia
authors.initials: P
authors.lastname: de Gortari
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Amaya
authors.forename: Milagros
authors.initials: M
authors.lastname: Méndez
mesh_terms: D000208:Acute Disease; D000428:Alcohol Drinking / Q000378:metabolism*; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism*; D000818:Animals; D018826:CD13 Antigens / Q000096:biosynthesis / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D008032:Limbic System / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D015260:Neprilysin / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000431:Ethanol; D018826:CD13 Antigens; D015260:Neprilysin