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