Withdrawal from chronic ethanol increases the sensitivity of presynaptic 5-HT(1A) receptors modulating serotonin and dopamine synthesis in rat brain in vivo.
The in vivo sensitivity of presynaptic 5-HT(1A) receptors (autoreceptors and heteroreceptors) modulating the synthesis of 5-hydroxytryptophan/serotonin (5-HTP/5-HT) and 3,4-dihydroxyphenylalanine/dopamine (DOPA/DA) in rat brain was investigated after ethanol treatment and withdrawal. In saline-treated rats as well as in acute ethanol (2 g/kg, intraperitoneally (i.p.), 2 h)- and chronic ethanol (2 g/kg for 7 days)-treated rats, a low dose of the 5-HT(1A) receptor agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT; 0.1 mg/kg, i.p., 1 h) did not decrease the synthesis of 5-HTP in brain (except modestly in striatum; 20% after the chronic treatment) or that of DOPA in striatum. In contrast, in chronic ethanol-withdrawn rats (24 h), 8-OH-DPAT significantly decreased the synthesis of 5-HTP in the hippocampus (29%), cerebral cortex (41%) and striatum (33%) and that of DOPA in the striatum (28%). Similar effects were induced by the mixed 5-HT(1A) agonist/D(2) antagonist buspirone (1 mg/kg, i.p., 1 h) which also decreased 5-HTP synthesis in the hippocampus (24%), cerebral cortex (36%) and striatum (35%) of chronic ethanol-withdrawn rats. These results indicate that chronic ethanol and more clearly the spontaneous withdrawal from chronic ethanol induce supersensitivity of 5-HT(1A)-auto/heteroreceptors modulating the synthesis of 5-HT and DA in rat brain.
Esteban
Susana
S
Laboratory of Neuropharmacology, Associate Unit of the Institute Cajal/CSIC, Department of Biology, University of the Balearic Islands, Carreterra Valldemossa Km 7.5, 07071 Palma de Mallorca, Spain.
Moranta
David
D
Sastre-Coll
Antoni
A
Miralles
Antonio
A
García-Sevilla
Jesús A
JA
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002065:Buspirone / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D002908:Chronic Disease; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis*; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D002065:Buspirone; D004298:Dopamine