Effects of subchronic lithium chloride treatment on G-protein subunits (G olf, Gγ 7) and adenylyl cyclase expressed specifically in the rat striatum

• Published in: European journal of pharmacology Vol. 428; no. 3; pp. 303 - 309
• Main Authors: Miki, Masahito, Hamamura, Takashi, Ujike, Hiroshi, Lee, Youmei, Habara, Toshiaki, Kodama, Masafumi, Ohashi, Kazuyo, Tanabe, Yasuyuki, Kuroda, Shigetoshi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12-10-2001; Elsevier
• Subjects: Adenylyl cyclase; Adenylyl Cyclases - drug effects; Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Blotting, Western; Body Weight - drug effects; Corpus Striatum - drug effects; Corpus Striatum - metabolism; G olf; Gene Expression Regulation - drug effects; GTP-Binding Protein alpha Subunits; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Gγ 7; Heterotrimeric GTP-Binding Proteins - drug effects; Heterotrimeric GTP-Binding Proteins - genetics; Heterotrimeric GTP-Binding Proteins - metabolism; In Situ Hybridization; Lithium - blood; Lithium chloride; Lithium Chloride - administration & dosage; Male; Manic–depressive illness; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Relapse; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Striatum; Time Factors; Striatum; Relapse; Manic–depressive illness; Adenylyl cyclase; Lithium chloride; G olf; Gγ 7; Subchronic; Rat; Enzyme; Psychotropic; Rodentia; Central nervous system; Oral administration; Phosphorus-oxygen lyases; Lithium; Lyases; Corpus striatum; Subunit; Adenylate cyclase; Vertebrata; Mammalia; Animal; Treatment withdrawal; Antipsychotic; Rebound; Mechanism of action; Withdrawal syndrome; Brain (vertebrata); G protein
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01343-7

Lithium salt has been widely used as a treatment for mania, but the mechanism of its effect remains unknown. Previously, by studying c-fos expression, we showed that the striatum was a possible target region for the antimanic effects of lithium salt. The present study focused on the effect of subchronic lithium chloride treatment on G-proteins (G
olf, Gγ
7) and adenylyl cyclase type V, which are expressed specifically in the rat striatum. Subchronic lithium chloride treatment significantly increased the level of G
olf protein, a stimulant α-subunit of G-protein, by 53.5% (
P<0.01), but the levels of Gγ
7 and adenylyl cyclase type V did not change. This increased level of G
olf protein was found after 2 weeks of lithium chloride treatment, but not after 1 week, and the level returned to the basal level 1 week after withdrawal of lithium chloride. This result suggests that the level of G
olf protein increases to compensate for the suppression of the adenylyl cyclase system by lithium, and that this increase may account for the “rebound” phenomenon, which is the relapse observed after abrupt discontinuation of lithium salt treatment.