CHRONIC ALCOHOL-CONSUMPTION AND WITHDRAWAL DO NOT INDUCE CELL-DEATH IN THE SUPRACHIASMATIC NUCLEUS, BUT LEAD TO IRREVERSIBLE DEPRESSION OF PEPTIDE IMMUNOREACTIVITY AND MESSENGER-RNA LEVELS

There is evidence that chronic ethanol treatment (CET) disrupts the bi ological rhythms of various brain functions and behaviors. Because the suprachiasmatic nucleus (SCN) is widely recognized as the dominant pa cemaker of the circadian system, we have examined the effects of CET a nd withdrawal on the main morphological features and chemoarchitecture of this hypothalamic nucleus. Groups of rats ethanol-treated for 6 an d 12 months were compared with withdrawn rats (ethanol-treated for 6 m onths and then switched to a normal diet for an additional 6 months) a nd with groups of age-matched control and pair-fed control rats. The v olume and the total number of neurons of the SCN were estimated from c onventionally stained material, whereas the total number of astrocytes and of neurons containing vasopressin (AVP), vasoactive intestinal po lypeptide (VIP), gastrin-releasing peptide (GRP), and somatostatin (SS ) were estimated from immunostained sections. The estimates were obtai ned using unbiased stereological methods, based on Cavalieri's princip le and the optical fractionator. The volume of the SCN and the total n umber of SCN neurons and astrocytes did not vary among groups. We foun d, however, that CET induced a significant reduction in the total numb er of AVP-, VIP-, GRP-, and SS-containing neurons. Withdrawal from alc ohol did not reduce but rather augmented the loss of VIP- and GRP-immu noreactive neurons. The CET-induced neurochemical alterations seem to result from a decrease in neuropeptide synthesis, as revealed by the r eduction in AVP and VIP mRNA levels demonstrated by in situ hybridizat ion with radioactively labeled 48-mer AVP and 30-mer VIP probes. It is thus possible to conclude that the irreversible CET-induced changes i n the neurochemistry of the SCN might underpin the disturbances in cir cadian rhythms observed after long-term alcohol consumption.