Anxiety and Fear Research on Rodents Elif Engin, MSc

Anxiety and Fear Research on
Rodents
Elif Engin, MSc
Graduate Student,
Depatment of Psychology, University of Alberta
What do we mean by anxiety in
animals?
 Built-in fear and
defense reactions
 Not necessarily a
conscious
experience of
“feeling”
The animal models that we use…
“unconditioned fear”
Elevated Plus-Maze
Anxiety measures:
 % Open arm time
 % Open arm entries
General Activity
Measures
 # Total arm entries
 # Closed arm entries
The animal models that we use…
Shock-Probe Burying
Anxiety measures:
Time spent burying
Latency to bury
General Activity measures:
Time still
Pain Sensitivity Measures:
Shock reactivity
The animal models that we use…
Social Interaction Test
Anxiety Measures:
Duration of social
interaction
(sniffing of conspecific, following of conspecific,
crawling under or over conspecific,
grooming, wrestling, kicking or boxing and
biting)
General Activity Measures
Number of line crosses
The animal models that we use…
Open Field Activity
Anxiety Measures
Amount of time spent in
the middle vs the edges
General Activity Measures
Number of line crosses
The animal models that we use…
Light-Dark Box
Anxiety Measures
Amount of time
spent in the light
chamber
Usually no control for
general activity
Other models of anxiety and fear
Fear Conditioning Paradigms
Eg, freezing response
Measures: Acquisition of the fear response
Acquisition of extinction
Renewal and generalization phenomena
Good for the study of some anxiety disorders
Confounds learning with anxiety
Brain Regions We are Interested In…
Amygdala
Septum
Hippocampus
Medial Prefrontal Cortex
Is “limbic system” actually a system?
Sample Studies and Findings:
Mapping the septo-hippocampal system
(eg, Degroot & Treit, 2001, 2002, 2003,
2004; Menard & Treit, 2001)
Anatomical background:
-Glutaminergic and GABAergic input into
septum from hippocampus
-Cholinergic and GABAergic projections
from septum to hippocampus via fimbria
fornix
Sample Studies and Findings:
Mapping the septo-hippocampal system
 Findings:
Inhibit acetylcholine breakdown
• in dorsal hippocampus (DH): Increased open arm activity
(OA), no effect on shock probe
• In ventral hippocampus (VH): Increased OA and more
shocks
Temporarily lesion
• DH: more shocks, no effect on OA or burying activity
• VH: increased OA, decreased burying, no effect on #shocks
• Septum: increased OA, decreased burying, no effect on
#shocks
• Fimbria fornix: increased OA, more shocks, no effect on
burying
Sample Studies and Findings:
Mapping the septo-hippocampal system
GABAA antogonist into septum
Increased OA, decreased burying
Combined subefective doses of septal
GABAA antagonist and DH
acetylcholinesterase inhibitor
decreased burying
Sample Studies and Findings:
Mapping the septo-hippocampal
system
 Conclusions:
 DH and VH affect fear reactions through cholinergic and
GABAergic mechanisms
 VH-cholinergic system is related to passive avoidance of
painful stimuli
 Both medial and lateral septum affect fear reactions
through GABAergic mechanisms
 Septal glutaminergic, hippocampal GABAergic, septal
GABAergic and hippocampal cholinergic systems interact
with each other in active and passive anxiety-related
behaviors
Sample Studies and Findings:
Medial Prefrontal Cortex
(eg, Shah & Treit, 2003, 2004; Shah, Sjovold &
Treit, 2004; Engin & Treit, 2005)
 Findings:
 Exitotoxic lesions of MPFC, microinfusions of
benzodiazepine-type and direct GABAA agonists,
microinfusions of D4 (but not D1 or D2) antagonists:
• Increased OA and social interactions
• Decreased burying
 Microinfusions of neurosteroid type GABAA agonist
allopregnanolone:
• Increased OA
• No effect on burying
Sample Studies and Findings:
Medial Prefrontal Cortex
Conclusions:
MPFC affects both active and passive fearrelated reactions through GABAergic and
Dopaminergic systems
Neurosteroid allopregnanolone modulates the
GABAergic system in a different way than the
benzodiazepines, affecting only the exploratory
responses
Sample Studies and Findings:
Inside the Amygdala
(eg, Treit, Pesold & Rotzinger, 1993; Pesold &
Treit, 1995; Engin & Treit, 2005)
Findings:
 Total amygdala lesions:
• No effect on OA activity or burying
• Increased shocks
 Total amygdala allopregnanolone microinfusions:
• Increased OA activity; no effect on burying
 Benzodiazepine microinfusions into
• Central amygdala: more shocks, no effect on OA activity
• Basolateral amygdala: increased OA activity, no effect on
number of shocks
• No effect on burying
Sample Studies and Findings:
Inside the Amygdala
Conclusions:
Basolateral amygdala is related to exploratory
fear-related responses
Central amygdala is related to passive
avoidance of painful/fearful stimuli
GABAergic amygdala system is involved in
those responses
In summary…
 Several brain structures, such as amygdala,
hippocampus, septum and MPFC are involved in
fear reactions
 Several neurotransmitter systems such as
GABAergic, cholinergic, dopaminergic and
glutaminergic systems are involved
 These structures affects different components of
defensive/fear-related behaviors
 These structures and neurotransmitter systems
interact in the production of these fear reactions