GABA mania

There is evidence for the contribution of serotonin dysfunction to mania, and in the mechanism of action of mood stabilizers [19], however, specific data on the serotonergic system and mania are fewer and variable. Moreover, altered functioning of other neurotransmitters in mania such as norepinephrine, dopamine, acetylcholine, and GABA, and their interaction with serotonin, are also likely to be involved in the pathogenesis of mood disorders. Differences in these neurotransmitter systems possibly underlie differences in the pathogenesis of depressive and manic episodes. 

Agents that increase GABA activity or decrease glutamate activity are used for the treatment of mania and for mood stabilization (eg, benzodiazepines, lamotrigine, lithiurn, or valproic acid). 

Use in combination with other drugs (e.g, anti-psychotics, lithium, valproate) for the acute treatment of mania or mixed episodes. Use as a short-term adjunctive sedativehypnotic agent. Binds to the benzodiazepine site and augments the action of GABA/, by increasing the frequency of Cl" channel opening which causes hyperpolarization (a less excitable state) and inhibits neuronal firing. 

Emrich HM, von Zerssen D, Kissling W, et al Effect of sodium valproate on mania the GABA hypothesis of affective disorders. Archiv fur Psychiatrie und Nervenkrankheiten 229 1-16, 1980... 

Carbamazepine is licenced as an alternative to lithium for prophylaxis of bipolar affective disorder, although clinical trial evidence is actually stronger to support its use in the treatment of acute mania. Carbamazepine appears to be more effective than lithium for rapidly cycling bipolar disorders, i.e. with recurrent swift transitions from mania to depression. It is also effective in combination with lithium. Its mode of action is thought to involve agonism of inhibitory GABA transmission at the GABA-benzodiazepine receptor complex (see also Epilepsy, p. 417). 

The catecholamine hypothesis of mood disorders suggests that increased DA and norepinephrine (NE) activity contribute to hyperactivity and psychosis associated with the severe stages of mania, and reduced activity causes depression. A y-aminobutyric acid (GABA) deficiency theory has been proposed for mania since it inhibits NE and DA activity. Glutamate and aspartate, excitatory amino... 

Even after years of research, it is still not clear which receptor sites or which monoamines are involved, although noradrenaline, serotonin and dopamine are all implicated. Neither does the theory explain how mania and depression can exist in the same patient. Much research has involved investigation of cerebrospinal fluid, blood and urine of patients to see if there are any abnormalities of monoamine metabolites. Although results may be complicated by diet, non-brain amines and the inevitable dmg therapy, evidence indicates that bipolar depression is associated with a decrease in dopamine activity, mania with an increase in dopamine activity [or depletion of inhibitory gamma-amino butyric acid (GABA)] and unipolar depression with a decrease in noradrenaline or serotonin activity or both. Levodopa (a precursor of dopamine) has been shown to produce symptoms of mania in patients with bipolar depression but not in those with unipolar depression. This still does not explain the swings in mood and little is known about how or why alternation between depression and mania occurs. 

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