CNS Transmission Flashcards
Sympathetic activation occurs by
noreadrenaline acting on alpha and beta adrenoceptors
Parasympathetic activation occurs by
ACh activating muscarinic receptors on peripheral, post-ganglionic neurons targeting tissue
GPCRs involve
second messenger systems, more visceral responses over seconds
Somatic activation occurs by
ACh acting on nicotinic receptors (ligand-gated ion channel)
What are the requirements for chemical neurotransmission?
synthesis and storage of NT; release of NT; inactivation of NT; and receptors (pre and post-junctional)
What are the targets for drug action on chemical neurotransmission?
enzymes, carriers, receptors, ion channels
What is the mechanism of inactivation of NA?
uptake
What is the mechanism of activation of ACh?
metabolism
Cocaine inhibits
neuronal re-uptake of noradrenaline
Amphetamine and ephedrine have what action on neuronal uptake?
substrates for uptake carrier - taken into nerve, displace NA, promoting its release
What are the neurotransmitter receptors within the CNS?
ligand-gated ion channels and GPCR
What are the types of CNS ligand-gated ion channels?
excitatory (nicotinic) - depolarize to Na+ influx; inhibitory (GABA A) hyperpolarize to Cl- influx
What type of receptors do NA and dopamine use?
GPCRs
What is the function of activation of GPCRs in the CNS?
activation of second messengers to modulate ion channel or enzyme activity
Post-synaptic NT receptors are located
in dendritic regions
Pre-synaptic NT receptors are located
in axon terminals
Post-synaptic NT receptors are involved in
AP generation and modulation
Pre-synaptic NT receptors are involved in
NT release
The noradrenergic system distributes to
cerebral cortex, cerebellum, descending pathways through brainstem to CV and respiratory centres - diffuse, widely acting
The noreadrenergic system produces
stimulant effects, mood, appetite, cardiovascular
The dopaminergic system distributes
more discretely than NA; cell bodies in substantia nigra, ventral tegmental area going up to striatum (motor control), frontal and prefrontal cortex (perception of environment), pituitary
Dopamine is involved in pathways for
movement (PD), behaviour (SCZ), dependence (via nucleus accumbens and ventral tegmental area), pituitary (prolactin)
Cocaine blocks uptake of
dopamine > noradrenaline and serotonin
Dopaminergic actions of cocaine are linked to
dependence (inhibits reuptake)
Noradrenergic/serotonergic actions of cocaine are the basis for
antidepressant drugs (inhibits reuptake)
Cocaine blocks what type of channels?
Na+ (at slightly higher concentrations) - basis for local anaesthetics
What is the general cause of Parkinson’s?
degeneration of dopaminergic pathways
What are the treatments for PD?
L-DOPA (precursor to dopamine) + peripheral dopa-decarboxylase inhibitor (inhibits peripheral conversion of dopamine); monoaminoxidase B inhibitors to decrease dopamine metabolism; dopamine receptor agonists; muscarinic receptor antagonists
What is the general cause of Huntington’s?
GABA deficiency
What are the treatments for Huntington’s?
Baclofen (GABA agonist); chlorpromazine (dopamine antagonist)
Glutamate is
excitatory
GABA is
inhibitory
Dopamine is
excitatory and inhibotry (receptor-dependent)
Serotonin is
excitatory and inhibitory (receptor-dependent)
Synapses in the CNS can be
excitatory OR inhibitory (depending on NT) but not both
How do astrocytes regulate signalling?
regulate GABA and glutamate levels; transfer AAs from blood to neurons
How are supporting cells involved in neuronal survival?
astrocytes - regulating neuron signalling (joins neuron to circulation, regulates GABA/glutamate, AAs); microglia - immune surveillance; generally, pH regulation and ECF homeostasis to maintain optimal CSF for neuronal firing; secretion of neurotrophic factors for development and survival
Neurotrophic factors act on
tyrosine kinase receptors
