Deficits in goal-directed motivation represent a debilitating symptom for many patients with schizophrenia. Impairments in motivation can arise from deficits in processing information about effort and or value, disrupting effective cost-benefit decision making. We have previously shown that upregulated dopamine D2 receptor expression within the striatum (D2R-OE mice) decreases goal-directed motivation. Here, we determine the behavioral and neurochemical mechanisms behind this deficit. Female D2R-OE mice were tested in several behavioral paradigms including recently developed tasks that independently assess the impact of Value or Effort manipulations on cost-benefit decision making. In vivo microdialysis was used to measure extracellular dopamine in the striatum during behavior. In a value-based choice task, D2R-OE mice show normal sensitivity to changes in reward value and used reward value to guide their actions. In an effort-based choice task, D2R-OE mice evaluate the cost of increasing the number of responses greater relative to the effort cost of longer duration responses compared to controls. This shift away from choosing to repeatedly execute a response is accompanied by a dampening of extracellular dopamine in the striatum during goal-directed behavior. In the ventral striatum, extracellular dopamine level negatively correlates with response cost in controls, but this relationship is lost in D2R-OE mice. These results show that D2R signaling in the striatum, as observed in some patients with schizophrenia, alters the relationship between effort expenditure and extracellular dopamine. This dysregulation produces motivation deficits that are specific to effort but not value-based decision making, paralleling the effort-based motivational deficits observed in schizophrenia.
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The authors are grateful to Tamara Azayeva and Hongfeng Jiang for technical help. This work was supported by the National Institute of Mental Health (NIMH) Grants: P50MH086404 (EHS) and R01MH068073 (P.D.B), The Lieber Institute for Brain Development and the German Academic Exchange Service, DAAD (IF).