Content of dynorphins and kappa-opioid receptors in distinct brain regions of C57BL/6 and DBA/2 mice.

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.