This study was supported by grants of the Italian Ministry of the University and Scientific Research (Murst) and National Research Council (CNR).
Differences in the Opioid System in Selected Brain Regions of Alcohol-Preferring and Alcohol-Nonpreferring Rats
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 23, Issue 8, pages 1296–1305, August 1999
How to Cite
Fadda, P., Tronci, S., Colombo, G. and Fratta, W. (1999), Differences in the Opioid System in Selected Brain Regions of Alcohol-Preferring and Alcohol-Nonpreferring Rats. Alcoholism: Clinical and Experimental Research, 23: 1296–1305. doi: 10.1111/j.1530-0277.1999.tb04350.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication December 17, 1998; accepted March 18, 1999.
- Opioid System;
- sP Rat;
- sNP Rat;
- Central Nervous System
Background: Previous studies have suggested that alcohol-reinforcing effects are mediated by the endogenous opioid system, which, in turn, stimulates mesolimbic dopaminergic neurotransmission. In addition, evidence obtained in 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 their innate alcohol preference (Sardinian preferring = sP) or alcohol aversion (Sardinian nonpreferring = sNP).
Methods: To evaluate whether differences observed were consequent to alcohol intake, sP rats were divided into two subgroups, ethanol-naive sP (sP) and ethanol-experienced sP (sPexp). Opioid receptors were labeled, using [3H]naloxone (μ, δ, and K receptors), [D-Ala2,N-Me-Phe4,Gly,ol5]enkephalin ([3H]DAMGO; μ receptors), and [D-Ala2,D-Leu5]enkephalin ([3H]DADLE; δ receptors), by means of quantitative autoradiography. Enkephalin and dynorphin mRNA contents were measured by in situ hybridization by using 25- and 47-base oligonucleotide probes with sequences complementary to mRNA encoding rat enkephalin or dynorphin.
Results: Our results revealed a significant reduction of opioid receptors in caudate-putamen nucleus and in the shell portion of the nucleus accumbens in sP compared with sNP rats. Alcohol intake partially reversed this reduction in the caudate-putamen nucleus. In addition, enkephalin mRNA expression 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 the brain areas examined.
Conclusions and Significance: Differences observed between the two lines of rats may implicate that genetic modifications in the opioid system are possibly responsible for the innate preference of sP rats toward alcohol intake. At the same time, it cannot be excluded that other functions might also be affected to some degree.