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The anxiolytic effect of ethanol is generally considered to be causally related to the development of alcohol dependence, and serotonin (5-HT) has been involved in both alcohol abuse and anxiety disorders. Several lines of evidence suggest an inverse relationship between alcohol abuse and central serotonergic neurotransmission.
When tested in the elevated plus-maze, selectively bred Sardinian alcohol-preferring (sP) rats display a higher degree of anxiety than Sardinian alcohol-non-preferring rats (sNP); this behavior is reversed by voluntary ethanol intake. The present study examined whether sP rats differed with respect to the 5-HT innervation in different forebrain areas.
We performed an immunohistochemistry study using an antibody raised against serotonin transporter (SERT), a marker for 5-HT fibers, coupled with an unbiased stereology, the method used to count the number of 5-HT neurons in the raphe nuclei.
The SERT-positive innervation density was found to be significantly lower in the medial-prefrontal cortex and in the shell of the nucleus accumbens of the ethanol-naive sP rats (sP-N) when compared with the sNP and unselected Wistar rats. No differences were found in the caudate putamen and hippocampus. The stereological analysis showed a significant difference in the number of 5-HT neurons in the dorsal but not in the median raphe of sP-N rats, compared with sNP and Wistar rats. Analysis of the cell body cross-sectional area revealed no differences among the three lines of rats either in the dorsal or in the median raphe. In sP rats that had voluntarily drunk ethanol for 14 consecutive days (sP-exp), no differences were found in the 5-HT innervation relative to sP-N animals.
These results indicate a selective reduction of innervation in the medial portion of the mesocorticolimbic 5-HT system in sP rats, suggesting that this genetically determined difference may be involved in the contrasting alcohol preference and consumption of sP and sNP animals.