Podcast
Questions and Answers
Which of the following mechanisms primarily contributes to the desensitization of receptors following chronic exposure to an agonist targeting a specific receptor?
Which of the following mechanisms primarily contributes to the desensitization of receptors following chronic exposure to an agonist targeting a specific receptor?
- Reduced receptor internalization and degradation
- Enhanced receptor insertion into the cell membrane
- Increased receptor phosphorylation leading to altered G-protein coupling (correct)
- Upregulation of receptor synthesis
A novel drug selectively inhibits the vesicular monoamine transporter 2 (VMAT2). What is the most likely consequence of this drug's action in neurons?
A novel drug selectively inhibits the vesicular monoamine transporter 2 (VMAT2). What is the most likely consequence of this drug's action in neurons?
- Reduced storage of monoamines in synaptic vesicles (correct)
- Increased release of dopamine into the synapse
- Enhanced reuptake of serotonin from the synaptic cleft
- Decreased degradation of catecholamines within the presynaptic neuron
Which of the following principles describes the primary mechanism by which general anesthetics such as volatile anesthetics and propofol, produce their anesthetic effects?
Which of the following principles describes the primary mechanism by which general anesthetics such as volatile anesthetics and propofol, produce their anesthetic effects?
- Blockade of excitatory neurotransmitter receptors (e.g., NMDA receptors)
- Inhibition of voltage-gated sodium channels, preventing action potential propagation
- Enhancement of inhibitory neurotransmission primarily mediated by GABA receptors (correct)
- Activation of opioid receptors in the CNS
Which of the following statements best describes the functional significance of the mesocortical dopaminergic pathway?
Which of the following statements best describes the functional significance of the mesocortical dopaminergic pathway?
A researcher is studying the effects of a novel compound on synaptic transmission in the hippocampus. Application of the compound leads to a rapid and transient increase in intracellular calcium within the postsynaptic neuron, followed by a prolonged enhancement of synaptic response to subsequent stimuli. Which type of receptor is most likely involved in mediating these effects?
A researcher is studying the effects of a novel compound on synaptic transmission in the hippocampus. Application of the compound leads to a rapid and transient increase in intracellular calcium within the postsynaptic neuron, followed by a prolonged enhancement of synaptic response to subsequent stimuli. Which type of receptor is most likely involved in mediating these effects?
A patient is diagnosed with a rare neurological disorder characterized by the selective degeneration of neurons in the striatum that project to the globus pallidus. Which of the following neurotransmitter imbalances is most likely to result from this condition?
A patient is diagnosed with a rare neurological disorder characterized by the selective degeneration of neurons in the striatum that project to the globus pallidus. Which of the following neurotransmitter imbalances is most likely to result from this condition?
Which of the following mechanisms underlies the therapeutic effect of xanthines, such as caffeine and theophylline, in promoting arousal?
Which of the following mechanisms underlies the therapeutic effect of xanthines, such as caffeine and theophylline, in promoting arousal?
A researcher is developing a novel analgesic drug that selectively targets opioid receptors in the spinal cord. Which of the following mechanisms of action would be most effective in reducing pain transmission?
A researcher is developing a novel analgesic drug that selectively targets opioid receptors in the spinal cord. Which of the following mechanisms of action would be most effective in reducing pain transmission?
What is the primary role of histamine within the central nervous system (CNS)?
What is the primary role of histamine within the central nervous system (CNS)?
A patient presents with symptoms indicative of excessive glutamate activity in the central nervous system (CNS). Which of the following mechanisms would be most effective in mitigating glutamate-induced excitotoxicity?
A patient presents with symptoms indicative of excessive glutamate activity in the central nervous system (CNS). Which of the following mechanisms would be most effective in mitigating glutamate-induced excitotoxicity?
Which statement accurately describes the function of the tuberinfundibular dopaminergic pathway?
Which statement accurately describes the function of the tuberinfundibular dopaminergic pathway?
Which of the following best describes how atypical antipsychotics affect neurotransmission in the brain?
Which of the following best describes how atypical antipsychotics affect neurotransmission in the brain?
What is the fundamental role of orexin neurons in the regulation of sleep and wakefulness?
What is the fundamental role of orexin neurons in the regulation of sleep and wakefulness?
Which of the following describes the mechanism by which tricyclic antidepressants (TCAs) primarily exert their therapeutic effects?
Which of the following describes the mechanism by which tricyclic antidepressants (TCAs) primarily exert their therapeutic effects?
How do endocannabinoids typically affect neurotransmitter release within the central nervous system (CNS)?
How do endocannabinoids typically affect neurotransmitter release within the central nervous system (CNS)?
Within the context of chronic drug exposure, what compensatory mechanism does the brain employ in response to chronic receptor antagonism?
Within the context of chronic drug exposure, what compensatory mechanism does the brain employ in response to chronic receptor antagonism?
What is a key difference between GABA\subscript{A} receptors and GABA\subscript{B} receptors regarding their mechanism of action?
What is a key difference between GABA\subscript{A} receptors and GABA\subscript{B} receptors regarding their mechanism of action?
Which of the following accurately describes the role of the ventrolateral preoptic area (VLPO) in the regulation of sleep?
Which of the following accurately describes the role of the ventrolateral preoptic area (VLPO) in the regulation of sleep?
How does the neurotransmitter dopamine influence motor control, and which specific dopaminergic pathway is critically involved in this function?
How does the neurotransmitter dopamine influence motor control, and which specific dopaminergic pathway is critically involved in this function?
A novel compound reverses amphetamine's effects. Which mechanism is most likely responsible for the reversal of amphetamine's effects?
A novel compound reverses amphetamine's effects. Which mechanism is most likely responsible for the reversal of amphetamine's effects?
A patient with a history of alcohol abuse is admitted to the hospital. During withdrawal, he is given a medication that acts as an agonist at GABA\subscript{B} receptors. Which effect of this medication is most beneficial in managing his withdrawal symptoms?
A patient with a history of alcohol abuse is admitted to the hospital. During withdrawal, he is given a medication that acts as an agonist at GABA\subscript{B} receptors. Which effect of this medication is most beneficial in managing his withdrawal symptoms?
Which of the following best describes the role of 5-HT3 receptors in the context of chemotherapy-induced emesis, and how is this understanding utilized in treatment?
Which of the following best describes the role of 5-HT3 receptors in the context of chemotherapy-induced emesis, and how is this understanding utilized in treatment?
In a research trial, scientists discover a new compound that selectively enhances the activity of enkephalin-producing interneurons in the spinal cord. What therapeutic outcome would be most anticipated from this compound?
In a research trial, scientists discover a new compound that selectively enhances the activity of enkephalin-producing interneurons in the spinal cord. What therapeutic outcome would be most anticipated from this compound?
Which of the following mechanisms is most likely to explain how mutations in nicotinic acetylcholine receptors contribute to conditions such as autosomal dominant frontal lobe nocturnal epilepsy (ADNFLE)?
Which of the following mechanisms is most likely to explain how mutations in nicotinic acetylcholine receptors contribute to conditions such as autosomal dominant frontal lobe nocturnal epilepsy (ADNFLE)?
A patient is exhibiting symptoms of muscle rigidity, tremors, and postural instability. Which neurotransmitter imbalance is most likely responsible for these symptoms, and which brain region is primarily affected?
A patient is exhibiting symptoms of muscle rigidity, tremors, and postural instability. Which neurotransmitter imbalance is most likely responsible for these symptoms, and which brain region is primarily affected?
What is a key mechanism that defines the retrograde signaling of endocannabinoids at synapses?
What is a key mechanism that defines the retrograde signaling of endocannabinoids at synapses?
Which best describes how caffeine leads to arousal?
Which best describes how caffeine leads to arousal?
Which mechanism primarily contributes to memories?
Which mechanism primarily contributes to memories?
Reserpine, historically used to treat hypertension, has been shown to block vesicular transport of catecholamines and serotonin. What direct mechanism relates to the effects of reserpine?
Reserpine, historically used to treat hypertension, has been shown to block vesicular transport of catecholamines and serotonin. What direct mechanism relates to the effects of reserpine?
Which best defines Histamine's role in arousal?
Which best defines Histamine's role in arousal?
Which neurological disorder involves a loss of basal forebrain cholinergic neurons and can be induced by antimuscarinic drugs?
Which neurological disorder involves a loss of basal forebrain cholinergic neurons and can be induced by antimuscarinic drugs?
Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine treat which condition?
Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine treat which condition?
Loss of dopaminergic neurons leads to this disorder:
Loss of dopaminergic neurons leads to this disorder:
Ketamine directly contributes to:
Ketamine directly contributes to:
Which best describes the action of GABA\subscript{A} receptor activation?
Which best describes the action of GABA\subscript{A} receptor activation?
Activation of opioid receptors directly causes:
Activation of opioid receptors directly causes:
Overstimulation of this neurotransmitter causes excitotoxicity:
Overstimulation of this neurotransmitter causes excitotoxicity:
Which best describes a characteristic of GABA?
Which best describes a characteristic of GABA?
Blockade of dopamine receptors relate to:
Blockade of dopamine receptors relate to:
Which of the following scenarios best describes the functional consequence of a drug that selectively enhances the activity of glutaminase within presynaptic neurons?
Which of the following scenarios best describes the functional consequence of a drug that selectively enhances the activity of glutaminase within presynaptic neurons?
A researcher discovers a novel compound that selectively prevents the insertion of new AMPA receptors into the postsynaptic membrane following long-term potentiation (LTP). What effect would this compound likely have on synaptic plasticity and learning?
A researcher discovers a novel compound that selectively prevents the insertion of new AMPA receptors into the postsynaptic membrane following long-term potentiation (LTP). What effect would this compound likely have on synaptic plasticity and learning?
In a patient experiencing acute ischemic stroke, which of the following mechanisms contributes most significantly to neuronal damage via excitotoxicity in the penumbral region (the area surrounding the core infarct)?
In a patient experiencing acute ischemic stroke, which of the following mechanisms contributes most significantly to neuronal damage via excitotoxicity in the penumbral region (the area surrounding the core infarct)?
A research study identifies a mutation that impairs the function of GABA transporters in the brain. Which of the following is the most likely consequence of this mutation on synaptic transmission?
A research study identifies a mutation that impairs the function of GABA transporters in the brain. Which of the following is the most likely consequence of this mutation on synaptic transmission?
A novel drug selectively inhibits GABA-transaminase, the enzyme responsible for breaking down GABA in the synaptic cleft. What is the most likely effect of this drug on neuronal activity?
A novel drug selectively inhibits GABA-transaminase, the enzyme responsible for breaking down GABA in the synaptic cleft. What is the most likely effect of this drug on neuronal activity?
Which of the following best describes the mechanism by which benzodiazepines exert their therapeutic effects in treating anxiety and insomnia?
Which of the following best describes the mechanism by which benzodiazepines exert their therapeutic effects in treating anxiety and insomnia?
How would a drug that selectively inhibits the vesicular GABA transporter (vGAT) in inhibitory interneurons most likely affect synaptic transmission?
How would a drug that selectively inhibits the vesicular GABA transporter (vGAT) in inhibitory interneurons most likely affect synaptic transmission?
A patient with Huntington's disease experiences a progressive loss of striatal neurons that project to the globus pallidus. How does this neuronal loss contribute to the characteristic motor symptoms of the disease?
A patient with Huntington's disease experiences a progressive loss of striatal neurons that project to the globus pallidus. How does this neuronal loss contribute to the characteristic motor symptoms of the disease?
Which of the following best describes the mechanism underlying the therapeutic effect of donepezil, an acetylcholinesterase inhibitor, in patients with Alzheimer's disease?
Which of the following best describes the mechanism underlying the therapeutic effect of donepezil, an acetylcholinesterase inhibitor, in patients with Alzheimer's disease?
In the context of Parkinson's disease, which of the following pharmacological strategies aims to directly address the imbalance caused by the degeneration of dopaminergic neurons in the substantia nigra?
In the context of Parkinson's disease, which of the following pharmacological strategies aims to directly address the imbalance caused by the degeneration of dopaminergic neurons in the substantia nigra?
A researcher is investigating a compound that selectively activates presynaptic alpha-2 adrenergic receptors in the central nervous system. Which of the following effects would be most likely observed?
A researcher is investigating a compound that selectively activates presynaptic alpha-2 adrenergic receptors in the central nervous system. Which of the following effects would be most likely observed?
How do selective serotonin reuptake inhibitors (SSRIs) affect the function of 5-HT\subscript{1A} autoreceptors, and what is the consequence of this interaction on the therapeutic effects of SSRIs?
How do selective serotonin reuptake inhibitors (SSRIs) affect the function of 5-HT\subscript{1A} autoreceptors, and what is the consequence of this interaction on the therapeutic effects of SSRIs?
A patient is prescribed a drug that blocks histamine H1 receptors in the brain. What is the most likely primary side effect this patient would experience?
A patient is prescribed a drug that blocks histamine H1 receptors in the brain. What is the most likely primary side effect this patient would experience?
Which of the following mechanisms best explains how endocannabinoids mediate retrograde signaling at synapses in the central nervous system?
Which of the following mechanisms best explains how endocannabinoids mediate retrograde signaling at synapses in the central nervous system?
A researcher discovers that a novel compound selectively enhances the reuptake of endocannabinoids from the synaptic cleft into the presynaptic neuron. What is the most likely effect of this compound on synaptic transmission?
A researcher discovers that a novel compound selectively enhances the reuptake of endocannabinoids from the synaptic cleft into the presynaptic neuron. What is the most likely effect of this compound on synaptic transmission?
Flashcards
Excitation (neurons)
Excitation (neurons)
Increases the probability that a neuron membrane potential reaches threshold, causing it to fire an action potential.
Inhibition (neurons)
Inhibition (neurons)
Decreases the probability that a neuron will fire an action potential.
Vesicular transporters
Vesicular transporters
Different proteins used to transport neurotransmitters into synaptic vesicles.
VMAT
VMAT
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Reserpine
Reserpine
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Reuptake transporters
Reuptake transporters
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DAT
DAT
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NET
NET
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SERT
SERT
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SSRIs
SSRIs
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Receptor desensitization
Receptor desensitization
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Receptor sensitization
Receptor sensitization
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Up-regulation
Up-regulation
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Down-regulation
Down-regulation
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Voltage-gated ion channels
Voltage-gated ion channels
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Ligand-gated ion channels
Ligand-gated ion channels
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Metabotropic receptors
Metabotropic receptors
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Glutamate
Glutamate
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Excitotoxicity
Excitotoxicity
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PCP (angel dust)
PCP (angel dust)
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GABA
GABA
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Baclofen
Baclofen
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GABA-A receptor
GABA-A receptor
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GABA-B receptor
GABA-B receptor
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GABA-A receptor
GABA-A receptor
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Reticular Activating System (RAS)
Reticular Activating System (RAS)
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Cholinergic circuits
Cholinergic circuits
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Norepinephrine
Norepinephrine
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Serotonin (5-HT)
Serotonin (5-HT)
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Tuberoinfundibular pathway
Tuberoinfundibular pathway
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Nigrostriatal pathway
Nigrostriatal pathway
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Mesolimbic pathway
Mesolimbic pathway
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Mesocortical pathway
Mesocortical pathway
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Histamine Neurons
Histamine Neurons
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Endocannabinoids
Endocannabinoids
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Study Notes
Objectives of CNS Pharmacology
- The four basic types of ion channels can be described
- Potential sites of CNS drug action can be identified at the neuronal level
- Receptor changes that may occur after chronic exposure to receptor agonists or antagonists can be described
- Major neurotransmitters in the CNS, their predominant anatomical pathways, and associated disorders can be listed
- The drug-related importance of the extrapyramidal system, reticular activating system (RAS), hypothalamus, and medulla oblongata can be explained in considering drug action
- The six basic CNS functions affected by drugs, the structures involved, and the drugs that affect each function can be indicated
Synaptic Transmission
- There are 100 billion neurons in the CNS
- There are 1,000-10,000 synaptic connections per neuron
- Excitation increases the probability that the neuron membrane potential reaches the threshold and fires an action potential
- Inhibition decreases the probability
Sites of Drug Action in CNS
- L-Dopa is site 1
- Reserpine is site 2
- Phenytoin is site 3
- Amphetamine is site 4
- Diazepam is site 5
- Tacrine is site 6
- Clonidine is site 7
- SSRI is site 8
Neurotransmitter Vesicular Transporters
- There are four types of neurotransmitter vesicular transporters
- Acetylcholine is a type of neurotransmitter vesicular transporters
- Catecholamines & serotonin (VMAT) is a type of neurotransmitter vesicular transporters
- Reserpine blocks Catecholamines & serotonin (VMAT)
- Amphetamine reverses Catecholamines & serotonin (VMAT)
- Glutamate is a type of neurotransmitter vesicular transporters
- GABA & glycine is a type of neurotransmitter vesicular transporters
Neurotransmitter Reuptake Transporters
- Neurotransmitter Reuptake Transporters are different proteins than vesicular transporters
- Dopamine (DAT) is a type of Neurotransmitter Reuptake Transporters, Cocaine affects it
- Norepinephrine (NET) is a type of Neurotransmitter Reuptake Transporters, TCAs affects it
- Serotonin (SERT) is a type of Neurotransmitter Reuptake Transporters, SSRIs affects it
- Glutamate is a type of Neurotransmitter Reuptake Transporters
- GABA is a type of Neurotransmitter Reuptake Transporters
Adaptation to Chronic Drug Treatments
- For antagonists compensation causes up-regulation
- Chronic Antipsychotics block dopamine receptors, this induces the production of more dopamine receptors and produces hyperkinetic disorders
- For agonists compensation causes down-regulation
- There is a delayed onset of therapeutic effects of antidepressants which block serotonin uptake
Mechanisms of Receptor Desensitization/Sensitization include
- Receptor Phosphorylation
- Receptor Dephosphorylation
- Receptor Internalization
- Receptor Insertion into membrane
- Receptor Down-regulation
- Receptor Up-Regulation
Types of Ion Channels in CNS
- Voltage-gated ion channel
- Ligand-gated ion channel
- Metabotropic receptor
Neurotransmitters
- Different groups of neurons use different neurotransmitters
- These different groups tend to serve different CNS functions
- Pharmacological manipulation of different groups of neurons can alter different CNS functions
Classes of Neurotransmitters include
- Amino acids
- Excitatory
- Glutamate
- Inhibitory
- GABA
- Glycine
- Biogenic Amines
- Acetylcholine
- Serotonin
- Histamine
- Catecholamines
- Norepinephrine
- Dopamine
- Purines
- Adenosine
- ATP
- Neuropeptides
- Endorphins
- Substance P
- NO
- Endocannabinoids
- Anandamide
Amino Acid Neurotransmitters
- Glutamate
- GABA
Glutamate: Major Roles and Clinical Significance
- Major ubiquitous excitatory neurotransmitter
- Clinical Importance involves Learning & Memory
- Memories are stored by enhancing glutamatergic synaptic transmission via long-term potentiation (LTP)
- Sufficient influx of Ca2+ through NMDA receptors is required for this
- Epilepsy: imbalance in excitation and inhibition, some antiepileptics block glutamate receptors
- Dissociative anesthesia (amnesia, catatonia, and analgesia), Ketamine blocks NMDA receptors
- Drug abuse, PCP (angle dust) is NMDA receptor antagonist, reduces NMDA receptor activation can cause hallucinations
- Excitotoxicity Excessive stimulation increases Ca2+ influx causing neuronal damage and neurodegeneration
- Stroke
- Amyotrophic lateral sclerosis
- Multiple sclerosis
γ-aminobutyric acid (GABA)
- Major inhibitory neurotransmitter in Brain
- 2 groups of neurons
- Interneurons: local circuit neurons: neocortex, thalamus, striatum, hippocampus, cerebellum, spinal cord
- Projecting neurons Striatum globus pallidus thalamus/ substantia nigra
- Loss of these neurons in Huntington’s chorea
- Septum → hippocampus
- Substantia nigra → thalamus/superior colliculus
- Ventrolateral preoptic area → nuclei of reticular activating system (RAS)
- Sleep promoting neurons
Types of GABA Receptors
- GABAA: Fast inhibitory transmission
- ↑ Cl- channel hyperpolarizes neuron
- Decreases membrane resistance
- Modulatory sites for
- Benzodiazepines & Barbiturates
- GABAB: Slow inhibitory transmission
- Baclofen is an agonist of GABAB receptors and reduces muscle spasms by increasing inhibition in the spinal cord
Clinical Importance of GABA Receptors
- Epilepsy is treated with Benzodiazepines & barbiturates
- Anxiety Disorders
- Insomnia
- Agitation
- Alcohol Abuse
- Pain regulation
- Muscle Spasm regulation
Biogenic Amines
- Acetylcholine
- Catecholamines
- Norepinephrine
- Dopamine
- Serotonin
- Histamine
Cholinergic Neurons
- Local Interneurons exist in
- Neocortex, Striatum, Hippocampus
- Projecting neurons includes
- Brain stem to thalamus
- Basal forebrain to neocortex, hippocampus, amygdala
- Peripheral neurons include
- Autonomic, Motor
Cholinergic Circuits
- Nicotinic Receptors exhibit fast transmission
- Muscarinic Receptors exhibit slow transmission
- Modulates Includes:
- Sleep-wake cycles
- Arousal
- Attention
- Parkinsonism (real and drug-induced)
- Muscarinic receptors oppose the effects of dopamine in the striatum
- Loss of dopaminergic neurons causes striatal imbalance, which can be corrected by increasing dopamine or reducing muscarinic activity with muscarinic blockers.
- Memory
- Alzheimer's disease
- Loss of basal forebrain cholinergic neurons
- Antimuscarinic-induced delirium is associated with memory
- Alzheimer's disease
- Mutations in nicotinic channels Includes
- Autosomal dominant frontal lobe nocturnal epilepsy
- Congenital myasthenic syndromes
Norepinephrine
- Locus coeruleus projects to the neocortex, hippocampus, thalamus, cerebellum, spinal cord promoting attention & arousal
- Reticular formation projects to the hypothalamus, basal forebrain, spinal cord producing autonomic & endocrine regulation
Clinical Importance of NE
- Arousal, Attention, Sleep cycles as the LC efferents
- ADHD and Narcolepsy is treated with amphetamine-like compounds
- Cognition: norepinephrine enhances memory formation
- Certain tricyclic antidepressants like amitriptyline work by blocking the reuptake of norepinephrine
- Adrenergic stimulation of the hypothalamus decreases appetite
- Pain perception (spinal cord): Norepinephrine excites enkephalin-producing interneurons in the spinal cord which inhibits pain transmission
Serotonin (5-HT)
- Released by projecting neurons from different raphe nuclei
- Raphe nuclei project to the neocortex, thalamus, hypothalamus, amygdala, striatum
- Raphe nuclei also projects to the brain stem, cerebellum, spinal cord
- Actions mediated by ~14 different receptors subtypes
- Clinical uses:
- Depression
- Panic disorder
- Obsessive-compulsive disorder
- Treatment
- Selective-serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac)
- Migraine is treated with 5-HT agonists like sumatriptan
- Presynaptic 5-HT receptors block the release of vasodilatory peptides
- Postsynaptic 5-HT receptors cause direct vasoconstriction
- Chemotherapy-induced Emesis treated with Ondansetron which blocks 5-HT3 receptors in the vomiting center of the medulla to inhibit emesis
- Modulates Pain perception
- Serotonin from platelets stimulates pain sensory nerve endings
- Serotonergic neurons stimulate enkephalin neurons in the spinal cord to reduce pain transmission
- Schizophrenia
- Atypical antipsychotics block 5-HT2 receptors
- LSD is a 5-HT agonist
Dopamine Pathways and Functions
- Tuberoinfundibular pathway
- Origin: Hypothalamus
- Target: Pituitary
- Function: Inhibits prolactin synthesis & release
- Nigrostriatal pathway
- Origin: Substantia nigra
- Target: Striatum
- Function: Regulates motor planning & execution
- Mesolimbic pathway
- Origin: Ventral tegmental area (VTA)
- Target: Nucleus accumbens
- Function: Regulates goal-directed and reward behavior
- Mesocortical pathway
- Origin: VTA
- Target: Neocortex
- Function: Regulates working memory, executive functions, and attention
Clinical Importance of Dopamine
- Parkinson’s disease
- Neurodegeneration of DA neurons in SN results in a relative loss of dopaminergic activity in the nigrostriatal pathway which leads to Hypokinetic (reduced movement)
- Huntington’s Chorea
- Neurodegeneration of striatal GABAergic neurons results in a relative excess of dopaminergic activity in the nigrostriatal pathway, leading to hyperkinetic (excessive movement)
- Schizophrenia
- Relative excess of dopaminergic activity in mesolimbic/ mesocortical pathways
- Can cause Extrapyramidal side effects from Antipsychotics
- Drug Addiction
- Increase in dopamine in the mesolimbic pathway
- Hyperprolactinemia
Histamine
- Tuberomammillary nucleus of the posterior hypothalamus projects to the entire CNS
- Histamine regulates arousal
- Many drugs block histamine receptors, producing sedation
Opioid Peptides
- Regulation of pain pathways occur at spinal and supraspinal levels
- Clinical Uses
- Agonists like Morphine are used as analgesics
- Agonists are also important drugs of addiction
Adenosine Receptors
- ATP is a co-transmitter
- It is metabolized to adenosine upon release
- The buildup of extracellular adenosine in the brain causes drowsiness
- Xanthines (caffeine, theophylline) block adenosine receptors, producing arousal
Endocannabinoids
- Endocannabinoids are endogenous brain lipids derived from arachidonic acid
- Anandamide and 2-arachidonylglycerol (2AG) are Endocannabinoids
- Endocannabinoids are rapidly synthesized in response to increases in intracellular calcium from the stimulation of metabotropic receptors on postsynaptic membranes
- Cannabinoid Receptors
- Are G-protein coupled receptors
- Are often located on axon terminals
- Stimulation inhibits neurotransmitter release
- Endocannabinoids often work as retrograde messengers
- They are degraded with a Reuptake pump and intracellular degradation
Functions Modulated by Endocannabinoids
- Pain
- Control of movement
- Regulation of body temperature
- Emesis
- Appetite
- Learning and memory; Cognition
- Neuroendocrine control
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