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.
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.
Authors: Stephen M Taubenfeld; Elizaveta V Muravieva; Ana Garcia-Osta; Cristina M Alberini Journal: Proc Natl Acad Sci U S A Date: 2010-06-21 Impact factor: 11.205
Authors: Todor V Gerdjikov; Andrew C Giles; Shelley N Swain; Richard J Beninger Journal: Psychopharmacology (Berl) Date: 2006-10-18 Impact factor: 4.530