Effect of chronic lithium treatment on D2/3 autoreceptor regulation of dopaminergic function in the rat.
Dysregulation of mesolimbic dopamine (DA) neurotransmission has been implicated in bipolar disorder. DA release in the nucleus accumbens is reduced in rats treated chronically with the mood stabiliser lithium, and this effect is maintained for 3 days after withdrawal from the lithium treatment. We tested whether this decrease in DA release is due to an increase in D(2/3) autoreceptor sensitivity. In vivo microdialysis studies showed that in the shell of the nucleus accumbens, dialysate DA was decreased following chronic lithium treatment and 3 days after withdrawal from lithium treatment. The elevation of dialysate DA induced by local blockade of the terminal D(2/3) receptor was reduced in both lithium treated and lithium withdrawn groups. In vitro electrophysiology studies showed that chronic lithium treatment (and lithium withdrawal) did not alter either basal firing rate of DA neurones in the ventral tegmental area, or somatodendritic D(2/3) autoreceptor-mediated inhibition of firing. D(2) mRNA expression in the ventral tegmental area was unchanged by lithium treatment and lithium withdrawal. Our data suggest that the decrease in dopamine release in the nucleus accumbens induced by chronic lithium treatment is not the result of increased terminal or somatodendritic autoreceptor sensitivity or decreased firing rate of DA neurones.
Ferrie
Lindsey J
LJ
Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Gartside
Sarah E
SE
Martin
Katherine M
KM
Young
Allan H
AH
McQuade
Richard
R
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D017660:Autoreceptors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D018021:Lithium Chloride; D004298:Dopamine