Dopamine and incentive learning: A framework for considering antipsychotic medication effects

Abstract

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine

“…On the other hand, dopamine D2 blockade caused by haloperidol has also been shown to reduce the prediction-error-related BOLD response in the ventral striatum ). High degrees of striatal dopamine D2 receptor blockade by typical neuroleptics may thus interfere with the attribution of incentive salience to conditioned stimuli, i.e., incentive learning (Beninger 2006), and Paquet et al (2004) described a procedural learning deficit in haloperidol treated patients (6 mg), but not in patients receiving olanzapine (14 mg) or healthy controls.…”

Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders

“…It appears that typical antipsychotics alter cognitive tasks associated with dorsal striatum functioning but not cognitive tasks associated with mPFC functioning; vice versa, atypical antipsychotics alter cognitive tasks associated with mPFC functioning but not cognitive tasks associated with dorsal striatum functioning. The overall status of antipsychotics on neurocognitive integrity is discussed and summarized in a number of recent articles (Beninger et al 2003(Beninger et al , 2009Beninger 2006;Schlagenhauf et al 2008).…”

Regional Differences in the Action of Antipsychotic Drugs: Implications for Cognitive Effects in Schizophrenic Patients

“…However, many studies have tested schizophrenic patients treated with APDs on measures of learning and memory without determining whether the drug and not the disease itself or an interaction of the two was responsible for the observed deficits (e.g., Bilder et al 2000). This is an important concern since it is well known that DA receptor blocking drugs affect particular forms of learning and memory (see Beninger 2006). Squire and Knowlton (2000) provide a taxonomy for mammalian memory systems that includes two broad categories, declarative and nondeclarative.…”

“…Declarative memories are conscious; nondeclarative memories are nonconscious. One form of nondeclarative memory described by Squire and Knowlton (2000) is termed ''skills and habits''; DA-mediated incentive learning is most appropriately placed in this category (Beninger 2006) and will be the focus of the current discussion since all APDs are DA receptor blockers (Kapur 2000).…”