Topics: Serotonin, Neuron, Brain Pages: 17 (3215 words) Published: February 3, 2013
Lecture 12-Mechanisms of drugs Question 1

TCAs-Tricyclic antidepressants
Blocks reuptake of norepinephrine and serotonin
ie they linger for longer in the synapse and interact with receptors longer

SSRIs-Selective serotonin reuptake inhibitors
Block only serotonin (not NE) reuptake

MAOIs-Monoamine oxidase enzyme inhibitors (MAOIs)
* Block action of MAO enzymes – presynaptic terminal has increased levels of monoamine transmitters for release * Decrease in MAO activityIncrease in NT presynaptic terminalincreased concentration of NT transport of NT outside (high concentration) into neuron (normally low) slows down

* Present in liver, intestines & brain monoamine (serotonin, dopamine & norepinephrine) releasing neurons * Inactivates monoamines

Mimics GABA on the GABA-A receptor (binds and activates it)
This increases the time that GABA-A channels open
More Cl- comes in

Binds to GABA-A receptor, but can’t activiate it if GABA is not bound on receptor at the same time) This allows for increased frequency of channel opening
Cl- influx a bit over what GABA does alone

MorphineSlow to get across BBB
Heroin=2xMorphine+O2 Also crosses a lot faster through BBB
HeroinMore rapid + delivers more morphine into brain

CB1 receptor activates G-protien which activates Ca2+ channels allowing for homeostasis THC-CB1 receptor agonist
Rimonanbant-CB1 receptor antagonist

* Found mainly in tobacco
* Binds acetylcholinergic nicotinic (nACh) receptors
* Widespread in the CNS with ‘neuromodulatory’ ability * Main ‘addictive’ constituent in tobacco

* Blocks the dopamine, norepinephrine and serotonin transporters * Prevents NT reuptake

Main mechanisms:
1. Block dopamine (DAT), norepinephrine (NET) & serotonin (SERT) transporters 2. ‘Reverse transport’ of NTs via reuptake transporters 3. ‘Reverse transport’ of NTs via vesicular transporter 4. Inhibit MAO activity

5. This allows for Massive NT release
Affinity for reuptake transporters:
* Amphetamine – highest affinity for DAT & NET
* Methamphetamine – highest affinity for DAT & NET (but faster across BBB than amphetamine) * MDMA – highest affinity for SERT

* Adenosine receptor antagonist
* Adenosine builds up in the brain during wakeful hours, and when levels peak around night time, it promotes sleepiness by binding to adenosine receptors * Thus caffeine blocks this effect
* Induces NE & E release from adrenal glands

HomeostasisBrain “prefers” set amount of receptor stimulation

Drug that increases NT release
Excessively stimulates receptors
Neurons take receptors back in

Drug that decrease/block NT release
No receptor stimulation
Neurons express new receptors

Lecture 16-Neurobiology of disordersQuestion 2, Hint: Behavioural Tests

Neuropsychological tests
* Cognitive, motor, behavioural, language, and executive functioning * Limitations of brain imaging – cannot always provide insight into psychological functioning * Used in diagnosis of several disorders

* Monitoring effects of drug treatments
* Assessment of CNS lesions and/or seizure disorders before and after surgical interventions * Assessment after injury
Few examples -
* Wisconsin Card Sorting Task (reactive cognitive flexibility) * Alternative Uses Test (spontaneous cognitive flexibility) * Mini Mental State Exam
* Alzheimers Disease Assessment Scale

Benefits of animal models
* Controlled experiments – effects of genetic changes on behaviour & brain function * Genetically altered animals – study whole animal, discoveries in mechanisms that cell models cannot replicate (cognitive behavioural impact, motor functions etc) * Complex cognitive/behavioural phenomena can be...
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