What controls the fear response? Flashcards
Is fear good?
It is a useful and innate response
What do we do when exposed to threatening stimuli?
We freeze - the flight/fight reaction kicks in and we respond
first, we freeze, the assess the situation
What are anxiety disorders a product of?
Inappropriate fear responses - responding in an excessive or maladaptive way - phobias or panic disorder
constant fear related behaviour - generalised anxiety
Why do we study the maladaptive state?
It allows us to work out which processes are important in the healthy state
Is there evidence that GABA dysfunction leads to anxiety disorder?
Patients with panic disorder injected with flumazenil (gaba antagonist), can see the number of gabaA receptors
Patients with panic disorder have less benzodiazepine binding sites
They also lack sufficient inhibitory control in cortical and limbic regions to suppress appropriate fear responses - so have a panic attack
the frontal cortex shows hyperactive responsiveness during periods of anxiety
What are GABAa receptors?
Channel membranes, sit across a membrane, when GABA binds, changes the confirmation so chloride can flux- made up of 5 subunits. Lots of combinations depending on the subunit, all have different properties (when they open, for how long etc)
What drugs reduce anxiety?
Drugs which increase GABAa receptor activity - anxiolytic
agonists: alcohol and barbiturates
indirect agonist: benzodiazepines
What is the difference between barbiturates and benzodiazepines?
Barbiturates are direct agonists, so they activate GABA on their own, possible to overdose with this because activates GABA alone. Benzodiazepines modify GABA, so they have a subtle effect
What drugs increase anxiety?
Drugs which decrease GABAa receptor - anxiogenic
antagonist: flumazenil
inverse agonist: beta-CCM
What is the difference between an anxiolytic and an anxiogenic?
Anxiolytic - reduces anxiety
Anxiogenic - increases anxiety
What do benzodiazepines do?
Have a binding site on the GABAa receptor, modify the channel but don’t do anything alone, change the GABA response on the receptors - need them both together
in presence:
GABA molecules are more efficient at opening Cl- Chanel, more chloride, greater hyper polarisation, more inhibition
What happens as you increase the drug concentration of benzodiazepines?
The more of the drug you get, you get an anxiolyitic effect - highest activity from agonist, then a partial agonist - activity above baseline activity
Inverse agonist gives you the opposite, get less chloride, antigenic effect
What is the most popular drug and why?
Benzodiazepines because the safety profile is relatively good
Is there the right drug at the right dose?
The more receptors that is occupied from the drug, the different properties it has
low doses - anxiolytic action, higher doses - sedative effects
With the drugs, different action depending on what receptor is targeted, so a full agonist will produce greater side effects whereas a partial agonist, will have less (benzodiazepines) - get the best effect with a larger therapeutic window
What are the other effects of benzodiazepines?
They act as: anxiolytic anticonvulsant sedative muscle relaxant amnestic an ideal drug would only have the anxiolytic effect
