title: Regulation of α₂-adrenoceptor gene expression by chronic lithium treatment in rat brain.
abstract: One of the approaches for the treatment of bipolar disorder involves the coadministration of lithium, a mood stabilizer, with α₂-adrenoceptor antagonists possessing an antidepressant effect. Since lithium accelerates the recovery of α₂(D)-adrenoceptors following their irreversible inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), our aim was to examine if it could be to some changes in Adra2A gene expression which codifies these adrenoceptors. Animals were treated with lithium chloride (120 mg/kg i.p.) or saline once a day for 10 days. A group of lithium- or saline-treated rats was killed 48 h after the last injection. The remaining animals were treated with EEDQ and were killed at 0.25, 4 and 14 days following this administration. Total RNA was extracted from cerebral cortex and Adra2A gene expression was measured by RT-QPCR. The results show that chronic lithium raised the Adra2A gene expression (P < 0.05), and after EEDQ administration this expression decreased to the basal level. No change in Adra2A gene expression was detected in the saline-treated group. However, EEDQ administration produced an insignificant increase in α₂-adrenoceptors mRNA levels followed by a progressive decrease until basal levels. Lithium produced an overexpression of the Adra2A gene after chronic treatment that made the neuron ready to produce α₂-adrenoceptors to deal with their inactivation.
authors.affiliation: Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, L'Hospitalet de Llobregat, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Cuffí
authors.forename: R
authors.initials: R
authors.lastname: Artells
authors.forename: A
authors.initials: A
authors.lastname: Navarro
authors.forename: F
authors.initials: F
authors.lastname: Ciruela
authors.forename: L
authors.initials: L
authors.lastname: Carbonell
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D011804:Quinolines; D018341:Receptors, Adrenergic, alpha-2; C000470:EEDQ; D012313:RNA; D018021:Lithium Chloride