Anxiety and Fear Research on Rodents

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 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: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

Anxiety and Fear Research on Rodents