CNSforum The Lundbeck Institute

Depression: Mania

The dopamine pathways in mania

Dopamine is transmitted via three major pathways in the brain. In mania there is an increase in dopamine transmission from the substantia nigra to the neostriatum which is associated with increased sensory stimuli and movement. Dopamine activity in the other two pathways, from the ventral tegmentum and the tubero-infundibular, remains unchanged in mania compared with a non-diseased brain.

GABAergic pathways showing the effects of mania

GABA is the main inhibitory neurotransmitter in the central nervous system (CNS). GABAergic inhibition is seen at all levels of the CNS, including the hypothalamus, hippocampus, cerebral cortex and cerebellar cortex. As well as the large well-established GABA pathways, GABA interneurones are abundant in the brain, with 50% of the inhibitory synapses in the brain being GABA mediated. There is evidence that there is decreased GABA function in all GABAergic pathways in depressed and manic states.

The noradrenaline pathways in mania

The principal noradrenaline centres in the brain are the caudal nuclei and the locus coeruleus. The transmission of noradrenaline from both of these centres to all areas of the brain is thought to be increased in mania compared with a non-diseased brain.

The serotonin pathways in mania

The principal serotonin centres in the brain are the caudal and rostral raphe nuclei. The transmission of serotonin from both of these nuclei to all areas of the brain is thought to be increased in mania compared with a non-diseased brain.