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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”. - PowerPoint PPT Presentation
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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 ActivityAnxiety 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…
AmygdalaSeptumHippocampusMedial 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
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: Mapping the septo-hippocampal system
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
Conclusions: MPFC affects both active and passive fear-
related 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: Medial Prefrontal Cortex
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
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
Sample Studies and Findings: Inside the Amygdala
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