Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens. Issue 4 (18th October 2016)

• Record Type: Journal Article
• Authors: Can, Adem; Frost, Douglas O.; Cachope, Roger; Cheer, Joseph F.; Gould, Todd D.
• Is Part Of: Journal of neurochemistry. Volume 139:Issue 4(2016)
• Page Start: 576
• Page End: 585
• Publication Date: 2016-10-18
• Subjects: amphetamine -- dopamine -- fast‐scan cyclic voltammetry -- lithium -- mania; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13769
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre‐clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast‐scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter‐train intervals, or administering d ‐amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d ‐amphetamine‐induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long‐term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article onPage 520 . Abstract : Three weeks' treatment with the anti‐manic drug, lithium, reduced dopamine release in mouse nucleus accumbens evoked by 60 Hz, but not 20 Hz, electrical stimulation of the ventral tegmental area, and attenuated increases in 20 Hz‐evoked dopamine release following acute amphetamine administration. These data suggest that lithium stabilizes mood because it attenuates dopamine release only when it is abnormally high. Read the Editorial Highlight for this article onPage 520 .