RESUMEN
Differences in the activity of distinct components of the endogenous opioid system between ethanol-preferring and ethanol-avoiding animals may be important in controlling their voluntary alcohol consumption. The objective of the present studies was to compare the activity of two opioid peptide systems (enkephalin and beta-endorphin) in distinct regions of the brain, between the C57BL/6 and DBA/2 mice, using sensitive radioimmunoassays, in situ hybridization, and immunohistochemical techniques. The immunohistochemical studies indicated that there was no significant difference in the number of either beta-endorphin or enkephalin immunopositive cells between the C57BL/6 and DBA/2 mice. The in situ hybridization studies demonstrated a 27% higher content of proopiomelanocortin mRNA in the arcuate nucleus of the C57BL/6 than DBA/2 mice, p < 0.02. The content of proenkephalin mRNA was 25% higher in the nucleus accumbens, p < 0.005 and 23% higher in the caudate putamen, p < 0.01, of the C57BL/6 than DBA/2 mice. There was no significant difference in the content of beta-endorphin peptides in the distinct brain regions investigated. The content of met-enkephalin-arg6-phe7 in the nucleus accumbens and caudate was similar between the two strains of mice, while it was significantly lower in the amygdala, hippocampus, ventral tegmental area, and periaqueductal grey of the C57BL/6 than DBA/2 mice. Thus, there are significant differences in the activity of these two endogenous opioid peptide systems in distinct regions of the brain, between ethanol naive C57BL/6 and DBA/2 mice, which may play a role in controlling their alcohol consumption.
Asunto(s)
Alcoholismo/genética , Química Encefálica , Encefalinas/análisis , Proopiomelanocortina/análisis , Precursores de Proteínas/análisis , ARN Mensajero/análisis , betaendorfina/análisis , Animales , Núcleo Arqueado del Hipotálamo/química , Química Encefálica/genética , Cruzamiento , Encefalinas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Proopiomelanocortina/genética , Precursores de Proteínas/genética , ARN Mensajero/genética , betaendorfina/genéticaRESUMEN
Differences in the activity of various components of the endogenous opioid system under basal conditions and after ethanol exposure have been reported between strains and lines of animals showing either high or low ethanol consumption. The objective of the present studies was to investigate the presence of differences in (a) the density of kappa-opioid binding sites, (b) the content of prodynorphin mRNA, and (c) the content of dynorphin peptides in distinct brain regions between the C57BL/6 (ethanol-preferring) and the DBA/2 (ethanol-avoiding) mice. Results indicated that the C57BL/6 mice have a higher content of kappa-opioid binding sites and dynorphin A 1-13 in the amygdala, and dynorphin A 1-8 in the ventral tegmental area, whereas the DBA/2 mice presented a significantly higher content of kappa-opioid binding sites, prodynorphin mRNA, as well as dynorphin A 1-13 and dynorphin A 1-8 peptides in the nucleus accumbens and septum. In addition, the DBA/2 mice presented a higher content of kappa-opioid receptors in the periaqueductal gray and dynorphin A 1-13 and dynorphin A 1-8 in the caudate putamen. Because enhanced stimulation of the kappa-opioid receptors at the level of the nucleus accumbens has been associated with decreased dopamine release and aversive states, the higher content of kappa-opioid receptors, pro-dynorphin mRNA, and dynorphin peptides (the endogenous ligand of k-binding sites) in regions of the limbic system of the DBA/2 mice may play an important role in determining their low alcohol consumption.