Neurotransmitters and Inhibitory Actions

Glutamate and Glial Cells

• Released glutamate acts on post-synaptic glutamate receptors.
• Glutamate is converted to glutamine in glial cells by the enzyme glutamine synthetase.
• In glia, glutamine is converted back to glutamate by the enzyme glutaminase.

Vesicular Transport and Excitation

• High concentrations of glutamate in synaptic vesicles are maintained by the vesicular glutamate transporter (VGLUT).
• Nearly all tested neurons are excited by glutamate through activation of ionotropic and metabotropic receptors.

Ionotropic Receptors

• Three main types of ionotropic receptors: AMPA, Kainic Acid (KA), and NMDA.
• AMPA receptors (contain GluA2 subunit) are permeable to Na+ and K+, but not Ca2+; some interneurons without GluA2 are Ca2+ permeable.
• KA receptors are permeable to Na+ and K+, and can be Ca2+ permeable depending on subunit composition.
• Domoic acid from shellfish can cause poisoning through excitatory action on KA and AMPA receptors, leading to symptoms like seizures.
• NMDA receptors are ubiquitous in the CNS, allowing Na+, K+, and Ca2+ permeability; they require extreme depolarization to open.

Inhibitory Neurotransmitters

• GABA and Glycine serve as primary inhibitory neurotransmitters.
• GABA is the major neurotransmitter in the brain, while Glycine is predominant in the spinal cord.
• Picrotoxins block GABA's effects by binding to GABA-A receptors causing convulsions.

Diffuse Neuronal Systems

• These systems have broad distribution and varied activities, innervating multiple CNS regions.
• Neurotransmitters involved include norepinephrine, dopamine, and serotonin (5HT), affecting a range of functions like sleep, attention, and emotional states.
• Primarily activate metabotropic receptors for long-lasting synaptic effects.

Neurotransmitter Categories

• Excitatory neurotransmitters trigger action potentials.
• Inhibitory neurotransmitters inhibit action potential transmission.
• Major amino acid neurotransmitters include glutamate, GABA, and glycine.

Neuropeptides and Functions

• Neuropeptides co-exist with conventional neurotransmitters, influencing functions such as reproduction, social behavior, appetite, pain, and learning.
• Opioid peptides like enkephalins and endorphins are included.

Orexin/Hypocretins

• Produced in the hypothalamus, orexins are excitatory neurotransmitters that regulate wakefulness and energy homeostasis.
• Lack of orexin or its receptors leads to narcolepsy and disturbed sleep patterns.

Other Signaling Substances

• Endocannabinoids are psychoactive compounds affecting cognition and pain perception.
• Nitric oxide and purines (ATP, UTP, adenosine) also act as signaling molecules in the CNS.

Antidepressant Agents

• Major Depressive Disorder (MDD) presents with persistent depressed mood, loss of interest, sleep and appetite disturbances, and cognitive deficits.
• Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and escitalopram have varying half-lives and inhibit cytochrome P450 enzymes.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) include venlafaxine and duloxetine, treating pain disorders and anxiety.

Tricyclic Antidepressants (TCAs)

• TCAs like imipramine and amitriptyline are used for treatment-resistant depression.
• 5HT2 receptor modulators such as trazodone block 5HT2A receptors and are often prescribed as sleep aids.

Tetracyclic and Unicyclic Antidepressants

• Similar to TCAs but infrequently prescribed.
• Depression increases risks for coronary artery disease, diabetes, and stroke.

MDD Pathophysiology

• Monoamine hypothesis suggests low monoamine levels in MDD.
• Neurotrophic hypothesis emphasizes the role of neurotrophic factors in neural plasticity and resilience.
• Brain-derived neurotrophic factor (BDNF) links effective antidepressant therapy to neurogenesis and synaptic connectivity, particularly in the hippocampus, which is crucial for memory and hormone release regulation.

This quiz covers the role of inhibitory neurotransmitters like GABA and Glycine, and how drugs interact with them, leading to effects like convulsions.