Stimulation of protein kinase a activity in the rat amygdala enhances reward-related learning.
BACKGROUND
Drug addiction in humans is associated with abnormal metabolic activity within the amygdala and heightened control of behavior by drugs and drug-related (conditioned) stimuli. Drug-induced neuroadaptations, including activation of cAMP (cyclic adenosine monophosphate)-dependent protein kinase A (PKA), within the amygdala may contribute to the synaptic plasticity and reward-related learning that underlies pathologic behavior in addicted individuals.


METHODS
In this study, we tested the hypothesis that stimulation of PKA activity within the rat amygdala would facilitate the acquisition of Pavlovian approach behavior, a measure of reward-related learning.


RESULTS
Intraamygdala infusions of Sp-cAMPS (which activates PKA) produced concentration-dependent enhancements of the acquisition of approach to a conditioned stimulus that predicted water availability; intraamygdala infusions of cholera toxin (which elevates cAMP levels) produced a similar effect. Conversely, intraamygdala infusions of Rp-cAMPS, an inhibitor of PKA, impaired acquisition of approach behavior.


CONCLUSIONS
Together, these data demonstrate that stimulation of PKA activity in the amygdala can facilitate reward-related learning and suggest that neuroadaptative changes in the PKA pathway within this brain region may be a mechanism by which chronic drug abuse alters the control of behavior by drug-associated stimuli.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
J David
JD
Jentsch
Peter
P
Olausson
Eric J
EJ
Nestler
Jane R
JR
Taylor
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D002772:Cholera Toxin / Q000008:administration & dosage; D000242:Cyclic AMP / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007858:Learning / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage; D013873:Thionucleotides / Q000008:administration & dosage; D013997:Time Factors
D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D013395:Sucrose; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases