Influence of GABA mimetics and lithium on biochemical manifestations of striatal dopamine target cell hypersensitivity.
The potential mechanisms whereby GABA mimetics and the antimanic agent lithium stabilize dopaminergic transmission are discussed. Evidence is presented that GABA mimetics, and in particular progabide, affect dopamine-mediated events in the basal ganglia on at least three levels. First, they reduce dopamine neuron activity in both the basal and the activated states. Secondly, on a long-term basis, they antagonize the proliferation of striatal dopamine receptors subsequent to chronic neuroleptic treatment. Thirdly, they modulate the expression of dopamine receptor activation by acting distally to the dopaminergic synapse. Lithium and GABA mimetics have the last two properties in common. These effects may represent the biochemical basis for the therapeutic action of GABA mimetics in iatrogenic dyskinesias. Moreover, the similarity between the biochemical effects of GABA mimetics and lithium suggest that the former drugs may have a therapeutic potential in mania.
Scatton
B
B
Fage
D
D
Oblin
A
A
Zivkovic
B
B
Arbilla
S
S
Langer
S Z
SZ
Bartholini
G
G
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011954:Receptors, Dopamine; C017985:progabide; D013134:Spiperone; D005680:gamma-Aminobutyric Acid; D008094:Lithium; D006220:Haloperidol