GABAB receptors are up-regulated by chronic treatment with lithium or carbamazepine. GABA hypothesis of affective disorders?
The effects of lithium and carbamazepine on GABAA and GABAB receptors were examined. The binding of [3H]muscimol and [3H](-)-baclofen to synaptic membranes from rat brain was used to label GABAA and GABAB receptors, respectively. Neither the [3H]muscimol nor the [3H](-)-baclofen binding site was displaced by lithium or carbamazepine even at a concentration of 100 microM. A single treatment with either of these drugs did not induce any change in [3H]muscimol and [3H](-)-baclofen binding sites in the frontal cortex and hippocampus. [3H](-)-Baclofen binding sites were up-regulated in the hippocampus but not in the frontal cortex following chronic treatment with lithium or carbamazepine. These results suggest that one common mechanism of action of lithium and carbamazepine is mediated by GABAB receptors and that GABA is involved in the pathophysiology of affective disorders.
Motohashi
N
N
Department of Neuropsychiatry, Yamanashi Medical College, Japan.
Ikawa
K
K
Kariya
T
T
D000818:Animals; D001418:Baclofen / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D019964:Mood Disorders / Q000503:physiopathology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D009118:Muscimol; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D008094:Lithium; D001418:Baclofen