Differences in the opioid system in selected brain regions of alcohol-preferring and alcohol-nonpreferring rats

Background: Previous studies have suggested that alcohol-reinforcing effect s are mediated by the endogenous opioid system, which, in turn, stimulates mesolimbic dopaminergic neurotransmission. In addition, evidence obtained i n both humans and rats indicates that genetic factors may influence alcohol -drinking behavior. In the present study, we examined several components of the opioid system in selected brain regions of rats bred selectively for t heir innate alcohol preference (Sardinian preferring = sP) or alcohol avers ion (Sardinian nonpreferring = sNP). Methods: To evaluate whether differences observed were consequent to alcoho l intake, sP rats were divided into two subgroups, ethanol-naive sP (sP) an d ethanol-experienced sP (sPexp). Opioid receptors were labeled, using [H-3 ]naloxone (mu, delta, and kappa receptors), [D-Ala(2),N-Me-Phe(4), Gly, ol( 5)]enkephalin ([H-3]DAMGO; mu receptors), and [D-Ala2,D-Leu(5)]enkephalin ( [H-3]DADLE; delta receptors), by means of quantitative autoradiography. Enk ephalin and dynorphin mRNA contents were measured by in situ hybridization by using 25- and 47-base oligonucleotide probes with sequences complementar y to mRNA encoding rat enkephalin or dynorphin. Results: Our results revealed a significant reduction of opioid receptors i n caudate-putamen nucleus and in the shell portion of the nucleus accumbens in sP compared with sNP rats. Alcohol intake partially reversed this reduc tion in the caudate-putamen nucleus. In addition, enkephalin mRNA expressio n was found to be decreased in the ventral part of caudate-putamen nucleus and increased in the cerebral cortex of sP rats compared with sNP rats; no significant differences were found in dynorphin mRNA expression in any of t he brain areas examined. Conclusions and Significance: Differences observed between the two lines of rats may implicate that genetic modifications in the opioid system are pos sibly responsible for the innate preference of sP rats toward alcohol intak e. At the same time, it cannot be excluded that other functions might also be affected to some degree.