Chronic alcoholization alters the expression of 5-HT1A and 5-HT1B receptor subtypes in rat brain.
The expression of central 5-HT1A and 5-HT1B receptors was studied in several brain areas of rats subjected to a 2-week period of chronic alcoholization, followed by 18 h withdrawal. Quantitative autoradiography indicated that the ethanol treatment provoked an increase (approximately +30%) in the labeling by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and [3H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide ([3H]WAY-100635) of 5-HT1A autoreceptors in the dorsal raphe nucleus, accompanied by a concomitant decrease in the labeling of postsynaptic 5-HT1A receptors in the hippocampus (approximately -20%), anterior (approximately -30%) and posterior (approximately -32%) cortices. These changes were associated with a tendency toward an increase and decrease in 5-HT1A mRNA levels in the anterior raphe area and hippocampus, respectively, suggesting that the changes observed are due to modifications in 5-HT1A receptor protein synthesis. The autoradiographic labeling of 5-HT1B receptors by serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide ([125I]GTI) was found to increase (+55%) in the globus pallidus of alcoholized rats. Interestingly, a significant increase (+57%) in 5-HT1B receptor mRNA levels was observed in the striatum, which contains cell bodies of neurons projecting into the globus pallidus. These data suggest that altered sensitivity of chronically alcoholized rats to 5-HT1A and 5-HT1B receptor ligands may result from alcohol-induced changes in the transcription of the genes encoding these receptors.
INSERM U. 288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
I
I
Nevo
X
X
Langlois
A M
AM
Laporte
M
M
Kleven
W
W
Koek
L
L
Lima
C
C
Maudhuit
M P
MP
Martres
M
M
Hamon
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D013997:Time Factors
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D000431:Ethanol