Fig. 3: Flow chart summarising the molecular changes that have been reported in the LHb in preclinical models of depression.

Excitatory changes are shown in green, inhibitory changes are shown in red and the endocannabinoid system, a neural system influencing both inhibitory and excitatory systems, is shown in orange. Circles in grey illustrate the key efferent projections of the Hb of relevance to depression. AEA anandamide, AMPA α-amino-3-hydroxy-5-methyl-4-isoxazoldpropionic acid, ßCaMKII ß calmodulin-dependent kinase II, DNA deoxyribonucleic acid, eNOS endothelial nitric oxide synthase, Glu glutamate, GABA gamma aminobutyric acid, IL-4 interleukin-4, IL-6 interleukin-6, IL-1ß interleukin-1ß, iNOS inducible nitric oxide synthase, Kir4.1 inward rectifying potassium 4.1 channel, LHb lateral habenula, nNOS neuronal nitric oxide, NMDA N-methyl-D-aspartate, TNF-α tumour necrosis factor α, 2-AG 2- arachidonoylglycerol → activation, inhibition.