MoA of ketamine
• Ketamine works as a non-competitive antagonist of the N-Methyl-D-Aspartate
(NMDA) glutamate receptor.
Primary action:
• NMDA receptor antagonist (glutamate receptor, subtype of ionotropic receptor).
• Blocks the phencyclidine (PCP) site inside the NMDA receptor channel.
• This ↓ excitatory glutamatergic transmission.
Downstream effects:
• ↑ Glutamate release via disinhibition of GABA interneurons → paradoxically increases AMPA receptor stimulation.
• Neuroplasticity: AMPA activation triggers BDNF release and mTOR signalling, promoting synaptogenesis (thought to underlie rapid antidepressant effects).
• Opioid receptor interaction: Weak agonist at μ and κ opioid receptors (may contribute to analgesia).
• Monoaminergic effects: Some action on dopamine reuptake inhibition (psychotomimetic, rewarding effects).
• Sigma receptor interaction: May contribute to dissociation.
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3 High-Yield Facts (BNF / Maudsley / SPMM):
1. Ketamine in psychiatry – licensed as esketamine nasal spray (NICE 2020, restricted use) for treatment-resistant depression.
2. Rapid antidepressant effect – within hours, unlike SSRIs (weeks). But relapse is common without maintenance.
3. Exam distractor: While NMDA antagonism is the primary MoA, its antidepressant effects are linked to downstream AMPA activation and neuroplasticity, not just “blocking glutamate.”
What is the Dopamine Theory related to psychosis?
Hyperactive dopamine at D2 receptors in the mesolimbic pathway.
This theory suggests that excess dopamine activity contributes to the symptoms of psychosis.
What is the Glutamate Theory in relation to schizophrenia?
NMDA receptor hypofunction.
This theory posits that reduced activity of
NMDA receptors is linked to the pathophysiology of schizophrenia.
What does the Serotonin Theory state about schizophrenia?
5HT2A receptor hyperfunction in the cortex.
This theory indicates that increased serotonin activity at these receptors may be involved in the disorder.
What neurotransmitter’s overactivity is suggested to cause schizophrenia?
Glutamate.
While glutamate is essential for normal brain function, its overactivity is associated with schizophrenia.
What role does dopamine play in cognitive function?
Dopamine improves cognitive function.
This suggests that dopamine is critical for various cognitive processes, especially in the context of schizophrenia.
Fill in the blank: Hyperactive dopamine at D2 receptors in the ____ pathway is part of the Dopamine Theory.
mesolimbic
True or False: Glutamate plays a role in memory consolidation that is separate from its role in schizophrenia.
True
What are the three major neurotransmitter pathways linked to psychosis?
- Dopamine
- Glutamate
- Serotonin
These neurotransmitters are critical in understanding the mechanisms behind psychotic disorders.
Which brain region is most implicated in
PTSD pathophysiology?
Answer: Amygdala (overactive), with reduced prefrontal regulation
Explanation: PTSD involves amygdala hyperactivity, hippocampal volume reduction, and impaired prefrontal inhibition.
3 High-Yield Facts:
• Hippocampal atrophy correlates with memory deficits.
• Increased noradrenergic tone →
hyperarousal.
• Basis for treatments: SSRIs (serotonin) and a1 blockers (prazosin).
Fill in the blank: The default mode network
(DMN) is active when a person is not focused on the outside world and the brain is at …?
wakeful rest
Key regions of the DMN include the medial prefrontal cortex, posterior cingulate cortex, precuneus, and angular gyrus.
What pathway is the Locus Coeruleus part
of?
Noradrenergic pathway
The noradrenergic pathway is involved in the release of norepinephrine.
POMC is a precursor for which hormones?
- ACTH MSH)
- Beta-endorphin
- Alpha-melanocyte-stimulating hormone (a-MSH)
These hormones play roles in stress response and pain modulation.
Serotonin is a precursor for which neurotransmitter?
Melatonin
Melatonin regulates sleep-wake cycles.
The neurotransmitter GABA is synthesized from:
A. Glutamate
B. Glycine
C. Dopamine
D. Acetylcholine
E. Serine
Glutamate
Explanation: GABA is made from glutamate by glutamic acid decarboxylase (GAD)
a) Which vitamin is a cofactor for GAD? →
Vitamin B6 (Pyridoxine)
b) What does GABA do? → Inhibitory NT
What does L-Amino Acid Decarboxylase convert?
L-DOPA to dopamine
This conversion is critical in the synthesis of neurotransmitters.
A neuroscience lecture discusses mechanisms that regulate brain extracellular pH. It explains that despite metabolic activity producing acids, the brain maintains a relatively stable pH through rapid buffering systems in cerebrospinal fluid (CSF) and brain tissue.
Which system primarily maintains pH balance in the brain?
A. Phosphate buffer system
B. Protein buffer system
C. Bicarbonate–carbon dioxide (HCO₃⁻ / CO₂) buffer system
D. Renal ammonium buffer system
E. Lactate metabolism
✅ Correct answer
C. Bicarbonate–carbon dioxide (HCO₃⁻ / CO₂) buffer system
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Why the bicarbonate–CO₂ system is correct
The bicarbonate–carbon dioxide buffer system is the primary regulator of pH in the brain and CSF.
Mechanism:
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
Key features:
• CO₂ easily diffuses across the blood–brain barrier
• Carbonic anhydrase rapidly converts CO₂ to carbonic acid
• The ratio of bicarbonate to CO₂ determines pH
Regulation occurs through:
• Respiratory control of CO₂
• CSF buffering
Because CO₂ crosses the BBB quickly, ventilation rapidly influences brain pH.
A neuroscience lecture discussing the pathophysiology of schizophrenia highlights abnormalities in neuronal excitability and synaptic transmission. Researchers note that disruption of specific ion channels alters cortical signaling and contributes to cognitive deficits and psychosis.
Which type of ion channel dysfunction has been implicated in schizophrenia?
A. Sodium channels
B. Chloride channels
C. Calcium channels
D. Potassium channels
E. Proton channels
✅ Correct answer
C. Calcium channels
⸻
Why calcium channels are correct
Evidence from genetic and neurobiological studies implicates voltage-gated calcium channel dysfunction in schizophrenia.
Important findings:
• Genome-wide association studies (GWAS) repeatedly identify variants in CACNA1C
• CACNA1C encodes L-type voltage-gated calcium channels
• These channels regulate:
• neuronal excitability
• synaptic plasticity
• neurotransmitter release
Abnormal calcium signaling disrupts:
• dopamine pathways
• glutamate transmission
• cortical network connectivity
This contributes to:
• cognitive deficits
• negative symptoms
• psychosis
Which neurotransmitter is often associated with memory and learning in the context of the Papez circuit?
Acetylcholine
Acetylcholine plays a key role in learning and memory, particularly through projections from the basal forebrain to limbic structures including the hippocampus, a central component of the Papez circuit.
Important roles:
• Facilitates synaptic plasticity
• Enhances attention and encoding of new information
• Supports long-term potentiation (LTP) in the hippocampus
• Critical for memory consolidation
Degeneration of cholinergic neurons contributes to memory impairment in conditions such as Alzheimer disease, which is why cholinesterase inhibitors are used.
Which receptor type is most directly associated with memory and learning via glutamate?
A. GABA-A
B. NMDA
C. D2
D. H1
E. 5-HT1A
NMDA
Explanation:
NMDA receptors are crucial for long-term potentiation and synaptic plasticity — implicated in schizophrenia and excitotoxicity.
M3 receptor blockade is associated with:
A. Gynecomastia
B. Akathisia
C. Anticholinergic side effects
D. Serotonin syndrome
E. Orthostatic hypotension
Anticholinergic side effects
Explanation:
M3 blockade leads to dry mouth,
constipation, blurry vision, urinary retention.
Blockade of H1 histamine receptors may cause:
A. Parkinsonism
B. Akathisia
C. Weight gain and sedation
D. Prolactin increase
E. Seizures
Weight gain and sedation
Explanation:
H1 receptor blockade → increased appetite, sedation. Seen with clozapine, quetiapine, mirtazapine.
The nucleus accumbens is the origin of which neurotransmitter?
A. GABA
B. Acetylcholine
C. Glutamate
D. Noradrenaline
E. Histamine
GABA
Explanation:
Nucleus accumbens is a GABAergic structure involved in reward and reinforcement.
———
• The nucleus accumbens (part of the ventral striatum) contains predominantly GABAergic medium spiny neurons.
• It integrates dopaminergic input from the ventral tegmental area (VTA) (mesolimbic pathway), as well as glutamatergic input from the prefrontal cortex, hippocampus, and amygdala.
• Its output is primarily GABA, projecting to the ventral pallidum.
The locus coeruleus is the primary site of:
A. Serotonin
B. Acetylcholine
C. Dopamine
D. Noradrenaline
E. GABA
Noradrenaline
Explanation:
Located in the pons, it’s involved in arousal, stress, and panic responses.
