anxiety 2

Question 1

Discuss the physiological basis of anxiety, including the roles of key neurotransmitters and the function of the GABAA receptor in the mechanism of action for certain anxiolytic drugs.

Answer 1

Based on the sources, the physiological basis of anxiety involves several key neurotransmitters. The sources list Norepinephrine/nor adrenaline, Serotonin, Histamine (collectively referred to as Monoamines), GABA (gamma-aminobutyric acid), and Glutamate as key neurotransmitters in anxiety. GABA is highlighted as the most important inhibitory neurotransmitter in the brain.
The GABAA receptor plays a significant role in the mechanism of action of certain anxiolytic drugs. The GABA_A receptor is described as a superfamily of ligand-gated ion channels. This complex is made up of several sub-units that form a GABA/Cl- channel complex. The receptor has separate binding sites for various substances, including GABA, benzodiazepines, and barbiturates.
When GABA is released from nerve terminals, it binds to the GABA_A receptors on the post-synaptic membrane. This binding increases the Cl- conductance. Binding of GABA alone leads to moderate hyper-polarization of the post-synaptic membrane due to moderate chloride conductance.
Certain anxiolytic drugs, such as benzodiazepines, work by interacting with the GABA_A receptor. Benzodiazepines bind to their own specific site on the GABAA receptor. They potentiate the action of GABA but do not open the channel by themselves. By binding, benzodiazepines increase the affinity for GABA and lead to an increased opening frequency of the ligand-gated Cl- channels. This results in a higher chloride conductance and more significant hyper-polarization compared to when only GABA is bound. This interaction swings the balance towards more GABA activity, as GABA is the main inhibitory neurotransmitter. This potentiation of GABA’s effects is how benzodiazepines exert their anxiolytic action, providing rapid symptomatic relief from acute anxiety symptoms.
Other drug treatments for anxiety mentioned include those that affect norepinephrine and serotonin, such as Antidepressants (SSRIs and SNRIs) which inhibit reuptake of these neurotransmitters, and Buspirone, which is a serotonin 1a partial agonist. Beta adrenoceptor antagonists like propranolol are also mentioned for treating somatic symptoms of anxiety. However, the sources focus specifically on the GABA_A receptor mechanism in relation to drugs like benzodiazepines, classifying them as having a fast onset of action.