Effects of cyclic adenosine monophosphate response element binding protein overexpression in the basolateral amygdala on behavioral models of depression and anxiety.
BACKGROUND
Chronic antidepressant administration increases the cyclic adenosine monophosphate response element binding protein (CREB) in the amygdala, a critical neural substrate involved in the physiologic responses to stress, fear, and anxiety.


METHODS
To determine the role of CREB in the amygdala in animal models of depression and anxiety, a viral gene transfer approach was used to selectively express CREB in this region of the rat brain.


RESULTS
In the learned helplessness model of depression, induction of CREB in the basolateral amygdala after training decreased the number of escape failures, an antidepressant response. However, expression of CREB before training increased escape failures, and increased immobility in the forced swim test, depressive effects. Expression of CREB in the basolateral amygdala also increased behavioral measures of anxiety in both the open field test and the elevated plus maze, and enhanced cued fear conditioning.


CONCLUSIONS
Taken together, these data demonstrate that CREB expression in the basolateral amygdala influences behavior in models of depression, anxiety, and fear. Moreover, in the basolateral amygdala, the temporal expression of CREB in relation to learned helplessness training, determines the qualitative outcome in this animal model of depression.
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Tanya L
TL
Wallace
Kathryn E
KE
Stellitano
Rachael L
RL
Neve
Ronald S
RS
Duman
D000679:Amygdala / Q000378:metabolism* / Q000821:virology; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002352:Carrier Proteins; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000523:psychology; D005786:Gene Expression Regulation / Q000187:drug effects; D018014:Gene Transfer Techniques; D006380:Helplessness, Learned; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000928:Antidepressive Agents; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein