Anxiety Flashcards
(21 cards)
Generalised symptoms of anxiety disorders
Increased vigilance, inhibition of ongoing behaviour, physiological responses. Demonstrate cognitive biases, increased likelihood to interpret ambiguous stimuli as threatening and to attend threat-related cues.
How do such changes arise?
Dysfunctional regulation of the brain circuitry responsible for emotional learning. PFC - top down control of emotional salience. Amygdala- processes threatening stimuli in a bottom-up manner.
First evidence implicating amygdala
Kapp (1979) lesion of amygdala inhibits heart rate conditioning in rabbits
Wilensky (2006)
Functional inactivation of the central nucleus of the amygdala shown to impair fear conditioning. Anatomically restricted infusions of muscimol and protein synthesis inhibitor.
Name the 2 lesion studies
Kapp (1979), Wilensky (2006)
NMDAR
CPP antagonist to NMDAR inhibits fear learning. Convergence of neurons, signalling CS and US occurs in the LA.
Kienast (2008)
Demonstrated that level of connectivity between amygdala and PFC exhibits an inverse relationship with trait anxiety
Interaction between GABA and amygdala
LTP in the LA relies on strong inhibitory GABA-ergic network. Inhibiting the neuronal firing to inappropriate stimuli- this can be overcome by significant events.
Crestani (1999)
Heterozygous inactivation of the gamma2 subunit gene provides partial reduction in GABAA function in developing mouse brain. Mice exhibited increased anxiety-like behaviours in adulthood, with similarities to human GAD.
Hasler (2008)
PET study using flumazenil tagged with carbon 11 to measure BZD receptor binding potential. Was increased in parts of the frontal, temporal and cortices in subjects with panic disorder when compared to controls.
What subunits of GABAR mediate anxiety?
Alpha1 subunits mediate sedative and amnesiac effects of Benzos. Alpha2 responsible for anxiolytic effects.
Czobor (2010)
4 week study showing anxiolytic activity without associated side effects. Study terminated following hepatic complications.
Kawahara (1993)
Concentration of 5HT increases in amygdala in response to stress and fear.
Bechara (1995)
5HT2CR antagonists increase skin conductance responses to CS in humans
Other 5HT receptor action?
Agonists of 5HT1AR are anxiolytic in humans and animals, but knockout mice show increased anxiety-like behaviour.
Hariri (2002)
fMRI study showing right amygdala activation was higher in response to fearful faces in carriers of the s allele of the 5HTT.
Angsorge (2004)
Fluoxetine to transiently inhibit the action of 5HTT in early mouse development (P4-P21) finding abnormal behaviours in adult. - Decreased exploratory behaviour, impaired shock avoidance, effects dependent on 5HT-/-. Impaired brain development resulting from impaired 5HT funciton
Whats the optogenetics region called?
Bed nucleus of the stria terminalis.
Jennings (2013)
vBNST neurons project to the VTA. Shown through antidromic stimulation assay. Glutamatergic and GABA-ergic projection neurons. Optogenetically stimulate glutamatergic - aversive and anxiogenic behaviour. Activating GABA-ergic - rewarding and anxiolytic phenotype. Caveat- unphysiological
Kash (2016)
ChR2 selectively expressed in 5-HT neurons. Activation enhanced fear and anxiety, activates CRT neurons in BNST - inhibitory microcircuit that underlies aversive behaviour following exposure to SSR1. CRT1R antagonism enough to prevent SSRI-induced enhancements in aversive learning.
Mohler and Rudolph (2002)
In vivo point mutation strategy to demonstrate that alpha 1= sedation, amnesia, alpha 2= anxiolytic
