How drugs control the brain - L13 part 2 Flashcards
What is the serotonergic system
- Nine raphe nuclei in reticular formation with diffuse projections - each projects into a different part of the brain
Where do the descending projections of the serotonergic system go to
- Cerebellum and spinal cord(pain)
What is the ascending reticular activating system(with lC)
- A set of interconnected nuclei that form ascending pathways to the cortex
- LC - noradrenergic nucleus locus coeruleus
When do raphe neurons fire
- Fire during wakefulness
- Quiet during sleep
What are the functions of serotonergic system
- Mood
- Sleep
- Pain
- Emotion
- Appetite
What is the only serotonergic ionotropic receptor
- 5-HT3 R - opens channel that fluxes Na+, K+, Ca2+ (excitatory)
- Is a cation-selective ion channel, capable of mediating fast excitatory neurotransmission in the CNS and peripheral nervous system
Effect of fluoxetine(prozac) on the serotonergic system
- Increase serotonin function by preventing its uptake
- Treatment for depression and anxiety but depression is not a simple case of low serotonergic tone(effects not seen for 2-3weeks)
- Increased availability of serotonin triggering downstream pathways
- Long term modulatory effects
- Second messenger cascades, gene transcription etc
Biochemical effect of MDMA
- Ecstasy causes serotonin(and norepinephrine) transporters to run in reverse increased release of serotonin and blocked re-uptake
Effect of LSD
LSD - lysergic acid diethylamide hallucinogen causes a dreamlike state with altered sensory perceptions
How does LSD affect sertonergic receptors
- LSD potent agonist at 5HT1A receptors in raphe nucleus
- Hallucinogenic properties at 5HT2A receptors in prefrontal cortex
Describe the noradrenergic system
- Projections form the locus coeruleus throughout the brain
- Role in arousal and attention
What are the metabotropic adrenergic receptors
- Alpha adrenergic receptors
Alpha1 Gq
Alpha2 Gi - Beta adrenergic receptors
Beta1, 2 and 3 Gs
What conditions can agonists and antagonists of adrenergic receptors used for
- Cardiac arrhythmias
- Migraines
What type of receptors do agonists and antagonists of adrenergic receptors mostly act on?
- Mostly on smooth muscle receptors, particularly in the cardiovascular and respiratory systems
- Best activated by novel, non-painful stimuli
Location of adrenergic system
- Primarily in lateral tegmental area, projecting to thalamus and hypothalamus
- Acts on alpha and beta adrenergic receptors
Location of cholinergic system
- In the periphery, acetylcholine at NMK and synapses in the autonomic ganglia
Functions of Ach
- Skeletal NMJ
- Neuromuscular synapse between the vagus nerve and cardiac muscle fibres
- Synapses in the ganglia of the visceral motor system
- A variety of sites in the CNS
What is myasthenia gravis
- Autoimmune disease that destroys cholinergic receptors in the muscle - muscle weakness and eventual loss of muscle activity
What is alzheimer’s
- Loss of cholinergic neurons in the basal ganglia - possibly underlies deficits in memory associated with the disease
Can dysfunction of the cholinergic system result in nicotine addiction?
Yes :(
What is autosomal dominant nocturnal frontal lobe epilepsy associated with?
- Autosomal dominant nocturnal frontal lobe epilepsy associated with mutations in nicotinic receptor genes
Action of acetylcholinesterase inhibitors
- prolong action of acetylcholine at the synapse
- Treatment for alzheimer’s disease(eg physostigmine)
- Treatment for myasthenia gravis(neostigmine)
What are examples of acetylcholinesterase inhibitors
- Insecticides
- Chemical warfare agents eg sarin
What is effect of botox
- Prevents release of Ach at NMJ
What is the effect of latrotoxin
- Permanent release - depletes Ach at NMJ
What are the two types of acetylcholine receptors
- Muscarinic - metabotropic
- Nicotinic - ionotropic
What are the postganglionic effects of autonomic ganglion cells on smooth muscle, cardiac muscle, or glandular targets mostly mediated by
- Noradrenaline and Ach
What do sympathetic ganglion cells and parasympathetic ganglion cells typically release
- Sympathetic ganglion cells release mostly NE(but, cholinergic innervation of sweat glands)
- Parasympathetic ganglion cells typically release Ach
Give an example of a muscarinic receptor agonist and a muscarinic receptor antagonist
- Muscarine(agonist) found in poisonous mushroom amanita muscaria
- Atropine(antagonist) belladonna alkaloid extracted from deadly nightshade
What is an autoreceptor
- Type of receptor located in the membranes of of presynaptic nerve cells
- It serves as part of a negative feedback loop(as autoreceptor detects neurotransmitters released by its own neuron and acts to inhibit further release)
Effect of atropine on pupil size
- Pupil is dilated by atropine administration and becomes unresponsive to light
- Relaxation of the ciliary muscle causes paralysis of accommodation and near vision is impaired
Structure of nicotinic receptors(in muscle) - ionotropic
- 5 subunits surrounding a central pore
- Muscle receptor 2xalpha1, beta, delta and gamma subunits(neuromuscular junction NMJ)
What is curare
- Antagonist of nicotinic acetylcholine receptor - causes instant paralysis
Structure of nicotinic receptors(neuronal receptors)
- Heteromeric combnation of alpha 3,4,5 and beta 2,3,4 or 6
- Homomeric receptors alpha 7,8 or 9
- Alpha3 beta4 on autonomic ganglia
- Alpha4beta2 and alpha7 most common brain receptors
What is the histaminergic system responsible for?
- Arousal and attention
- Reactivity of vestibular system
- Mediation of allergic responses
- Influence of brain blood flow
- 3 G-protein coupled receptors
