Anxiety and Fear Research on Rodents

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Anxiety and Fear Research on Rodents

• Elif Engin, MSc
• Graduate Student,
• Depatment of Psychology, University of Alberta

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What do we mean by anxiety in animals?

• Built-in fear and defense reactions
• Not necessarily a conscious experience of
  feeling

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The animal models that we useunconditioned
fear

• Elevated Plus-Maze
• Anxiety measures
• Open arm time
• Open arm entries
• General Activity Measures
• Total arm entries
• Closed arm entries

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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
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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

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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

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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

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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

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Brain Regions We are Interested In

• Amygdala
• Septum
• Hippocampus
• Medial Prefrontal Cortex
• Is limbic system actually a system?

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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

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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

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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

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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

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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

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Sample Studies and Findings Medial Prefrontal
Cortex

• 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

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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

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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

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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