Immunocytochemical study of the forebrain serotonergic innervation in Sardinian alcohol-preferring rats.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Casu
Maria Antonietta
MA
Neuroscienze SCARL, Via Palabanda 9, 09125 Cagliari, Italy. mantonietta.casu@ns.crs4.it
Pisu
Carla
C
Lobina
Carla
C
Pani
Luca
L
D000437:Alcoholism / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000150:complications*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013045:Species Specificity
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D000431:Ethanol