title: Impairments of probabilistic response reversal and passive avoidance following catecholamine depletion.
abstract: Catecholamines, particularly dopamine, have been implicated in various aspects of the reward function including the ability to learn through reinforcement and to modify flexibly responses to changing reinforcement contingencies. We examined the impact of catecholamine depletion (CD) achieved by oral administration of alpha-methyl-paratyrosine (AMPT) on probabilistic reversal learning and passive avoidance (PA) in 15 female subjects with major depressive disorder in full remission (RMDD) and 12 healthy female controls. The CD did not affect significantly the acquisition phase of the reversal learning task. However, CD selectively impaired reversal of the 80-20 contingency pair. In the PA learning task, CD was associated with reduced responding toward rewarding stimuli, although the RMDD and control subjects did not differ regarding these CD-induced changes in reward processing. Interestingly, the performance decrement produced by AMPT on both of these tasks was associated with the level of decreased metabolism in the perigenual anterior cingulate cortex. In an additional examination using the affective Stroop task we found evidence for impaired executive attention as a trait abnormality in MDD. In conclusion, this study showed specific effects of CD on the processing of reward-related stimuli in humans and confirms earlier investigations that show impairments of executive attention as a neuropsychological trait in affective illness.
authors.affiliation: Department of Psychiatry, University Hospital, Zurich, Switzerland. g.hasler@bluewin.ch
authors.forename: Gregor
authors.initials: G
authors.lastname: Hasler
authors.forename: Krystal
authors.initials: K
authors.lastname: Mondillo
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.forename: James R
authors.initials: JR
authors.lastname: Blair
mesh_terms: D000293:Adolescent; D000328:Adult; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism / Q000523:psychology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012193:Reversal Learning / Q000187:drug effects*; D012201:Reward; D057190:Stroop Test; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D019788:Fluorodeoxyglucose F18; D019805:alpha-Methyltyrosine
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