Lecture 2- Brain substrates Flashcards
What are Catecholamines (Name 4)?
A group of drugs that affect neurotransmitters
-Dopamine= Amphetamines, Cocaine -Noradrenalin= Amphetamines, Cocaine -Serotonin= MDMA -Acetylcholine= Nicotine
What are neurotransmitters and hormones derived from?
The amino acid Tyrosine
What do enzymes do to the Catecholamines?
They turn the aspects into the next level as all steps in process can be interfered w/ eg missing enzymes
-Tyrosine > DOPA > Dopamine > Noradrenaline > Adrenaline
What role do Catecholamines play?
They play key roles in stress responses, blood pressure regulation, metabolic processes
What is the lock and key method in Catecholamines?
Receptors expect a specific (often dopamine) key and once they become full, they become full agonists for receptors to pass electrical signal (lock + key)
How does hacking Catecholamines work?
Within the lock and key method, other compounds are similar/mimic shape of agonists so will fit into gap
-This means the agonists eg dopamine can no longer fit.
What do the Cocaine, Amphetamines, Risperidone and Ritalin drugs do within the lock and key mechanism?
Cocaine= Inhibits DA & NA transporters Amphetamines= Increased DA & NA release Risperidone= Blocks DA receptors Ritalin= Blocks DA & NA uptake
What is Resperine in regards to Catecholamine?
A catecholamine antagonist that inhibits VMAT (protein responsible for moving back to vesicles) (hacking catecholamines)
What are dopamine pathways?
They are neural circuits which have specialised dopamine paths in which dopamine travels through to regulate physical & psychological functions
They can also be considered chains of neutrons across the body that move the Catecholamine system
What are dopamine pathways key for?
Critical for key processes eg movement, reward, hormonal control
What does the mesocortical pathway do?
Regulates cognition, decision making, social behaviour (individualisation)
Where does the mesocortical pathway work?
Originates in VTA but projects to the frontal cortex
What does dysfunction/underactivity in the mesocortical pathway create?
Dysfunction/under activity is associated w/ negative sz symptoms + cog impairments
-Low dopamine levels in pathway leads to depression, apathy so using drugs it can pump up dopamine levels to reduce symptoms.
What do drugs do in the mescocortical pathway?
Aim to increase dopamine activity in prefrontal cortex (PFC).
-Address cog dysfunction, emotional regulation, neg symptoms in conditions such as sz, ADHD Eg Risperidone which promotes DA in PFC
What does the mesolimbic pathway do?
-It’s the main pathway involved w/ addiction
-Involved in reward/motivation and pleasure feeling so plays central role in reinforcing behaviours and addiction development.
Where does the mesolimbic pathway work?
Originates in VTA but projects to nucleus accumbens and other limbic areas eg amygdala
What does overactivity in the mesolimbic pathway create?
Overactivity in pathway can lead to pos sz symptoms & other reward processing disorders
What do drugs do in the mesolimbic pathway?
They are crucial for motor control
-Low dopamine in the nigrostriatal pathway → Parkinson’s disease, drug-induced Parkinsonism. -Excess dopamine in the nigrostriatal pathway → Tardive dyskinesia, Huntington’s chorea.
What does the Tuberoinfundibular pathway do?
-Regulates secretion of prolactin from anterior pituitary gland, playing key role in hormonal control.
Where does the Tuberoinfundibular pathway work?
-Originates in hypothalamus and projects to pituitary gland.
What does dysfunction create in the Tuberoinfundibular pathway?
-Dysfunction can result in hyperprolactinemia eg infertility
What do drugs do in the Tuberoinfundibular pathway?
-DA acts as a prolactin antagonist but increased prolactin can lead to infertility, decreased libido. -Decreased prolactin is very rare and not clinically signif unless in conditions like hypopituitarism.
How can you target drugs?
DA has multiple receptors: D1-like, D2-like
-There are multiple locks for the same key
-Some activate easily (D3), and others less so (D1), some excite the neuron (D1-like), while others calm it down (D2-like).
-They are often located in diff regions eg D1-movement, D3-impulse control
What happened in the beyond drugs Xu, Guo, Vorhees & Zhang, (2000) study?
Mutant mice lacking D1 receptors are insensitive to cocaine which increased locomotor activity in the wild-type but not the knockout mice.
What attempted to combat side effects in the Giros et al (1996) study?
They genetically engineered mice to have no dopamine transporter
-An animal under treatment to become more hyperactive will respond by wanting more of that treatment, suggesting it’s rewarding and showing addiction potential.
