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Emotions and the brain
Sub-Topics
Fear, Anxiety and Anguish

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Help Linked Module: Clinical Application: GABA and Anxiety Linked Module: The complexion of fear Linked Module: The Genetics of Fear
Linked Module: Is our tendency to experience fear and anxiety genetic?

The first synthetic benzodiazepines were marketed by Hoffmann-La Roche in 1960, with chlordiazepoxyde (Librium) followed in 1963 by diazepam (Valium). Now there are some fifty different commercial forms.

Another category of medications that act on serotonin levels are the serotonin-specific reuptake inhibitors (SSRIs), the most famous of which is Prozac (generic name: fluoxetine). These molecules prevent serotonin from being reabsorbed by the presynaptic neuron after it has been released into the synaptic gap. Initially this results in an increase in the amount of serotonin in the synapse. In the longer run, it reduces the neurons’ serotonin content.

Linked Module: Positive Neuromodulation of GABAa Receptors: Tranquilizers Linked Module: Serotonin Reuptake Blocking Agents (SSRIs)


ANXIETY NEUROTRANSMITTERS
GABA RECEPTORS

Since scientists discovered the mechanism by which benzodiazepines act to alleviate anxiety, all the evidence has indicated that the neurotransmitter GABA and its receptors play a fundamental role in controlling anxiety.

 

After benzodiazepines are ingested, they bind to a specific site on the GABA receptor. The presence of benzodiazepine on this site potentiates the effect of the GABA, further diminishing the brain hyperactivity associated with anxiety.

 

As happens with many drugs, some endogenous molecules analogous to benzodiazepines have been isolated in the brain. These molecules appear to be a natural means of adjusting the neuron-inhibiting action of GABA.

Various aspects of anxiety also seem to be influenced by other systems of neurotransmitters. Many laboratories are investigating the role of serotonin in particular. This molecule, produced mainly in the Raphe nuclei in the brainstem, is known for its modulating effect on appetite, sleep, mood, libido, and cognitive functions. All of these functions are disturbed by anxiety.

The hypothesis that serotonin plays a role in anxiety is also supported by the close connections between this neurotransmitter and the locus coeruleus, the centre of norepinephrine production in the brain, which has very dense projections to the amygdala. In fact, the serotonin and norepinephrine systems are so closely bound together by numerous reciprocal connections that a modification in one inevitably affects the other.

It is also known that the effect of norepinephrine on the amygdala’s beta-adrenergic receptors causes emotionally charged events to be recorded more permanently in memory.

       

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Linked Module: Le récepteur GABA
GABA RECEPTORS
ANXIETY NEUROTRANSMITTERS

Because GABA is the primary inhibitory neurotransmitter in the mammalian nervous system, it is involved in a great many physiological functions. This decrease in neural activity is achieved by means of the GABA receptor which, when activated by GABA, hyperpolarizes the neuron, thus favouring the influx of negatively charged chloride ions.

Several different pharmacological substances can modulate the effect of GABA by binding to GABA receptors. These substances include benzodiazepines, barbiturates, picrotoxin, certain steroids, and even alcohol, and they bind to the receptor at different sites from the GABA itself.  

These substances are called GABA modulators because they increase or decrease the effect of GABA, but have no effect in the absence of GABA. Those GABA modulators that reduce the effectiveness of GABA, and hence the neural membrane’s permeability to chloride ions, have an anxiogenic effect. Conversely, those GABA modulators that increase the effectiveness of GABA, and hence the neural membrane’s permeability to chloride ions, have an anxiolytic effect. This latter group includes the benzodiazepines, which are the most powerful potentiator of chloride permeability and hence of GABA’s inhibitory effect.

Molecular biologists have isolated at least three types of GABA receptors that are themselves formed of several complex proteic sub-units.

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