The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine

Sofia Cussotto, John F. Cryan, Olivia F. O’Leary
Neuroscience Letters. 2017-05-01; 648: 14-20
DOI: 10.1016/j.neulet.2017.03.040

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1. Neurosci Lett. 2017 May 1;648:14-20. doi: 10.1016/j.neulet.2017.03.040. Epub
2017 Mar 27.

The hippocampus and dorsal raphe nucleus are key brain areas associated with the
antidepressant effects of lithium augmentation of desipramine.

Cussotto S(1), Cryan JF(1), O’Leary OF(2).

Author information:
(1)Department of Anatomy and Neuroscience, University College Cork, Cork,
Ireland; APC Microbiome Institute, University College Cork, Ireland.
(2)Department of Anatomy and Neuroscience, University College Cork, Cork,
Ireland; APC Microbiome Institute, University College Cork, Ireland. Electronic
address: .

Approximately 50% of depressed individuals fail to achieve remission with
first-line antidepressant drugs and a third remain treatment-resistant. When
first-line antidepressant treatment is unsuccessful, second-line strategies
include dose optimisation, switching to another antidepressant, combination with
another antidepressant, or augmentation with a non-antidepressant medication.
Much of the evidence for the efficacy of augmentation strategies comes from
studies using lithium to augment the effects of tricyclic antidepressants. The
neural circuitry underlying the therapeutic effects of lithium augmentation is
not yet fully understood. Recently, we reported that chronic treatment with a
combination of lithium and the antidepressant desipramine, exerted
antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that
did not exhibit an antidepressant-like behavioural response to either drug
alone. In the present study, we used this model in combination with ΔFosB/FosB
immunohistochemistry to identify brain regions chronically affected by lithium
augmentation of desipramine when compared to either treatment alone. The data
suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal
hippocampus are key nodes in the neural circuitry underlying antidepressant
action of lithium augmentation of desipramine. These data give new insight into
the neurobiology underlying the mechanism of lithium augmentation in the context
of treatment-resistant depression.