Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Methods The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. Results APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. Conclusions We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies

Role of Kv1 Potassium Channels in Regulating Dopamine Release and Presynaptic D2 Receptor Function

Dopamine (DA) release in the CNS is critical for motor control and motivated behaviors. Dysfunction of its regulation is thought to be implicated in drug abuse and in diseases such as schizophrenia and Parkinson's. Although various potassium channels located in the somatodendritic compartment of DA neurons such as G-protein-gated inward rectifying potassium channels (GIRK) have been shown to regulate cell firing and DA release, little is presently known about the role of potassium channels localized in the axon terminals of these neurons. Here we used fast-scan cyclic voltammetry to study electrically-evoked DA release in rat dorsal striatal brain slices. We find that although G-protein-gated inward rectifying (GIRK) and ATP-gated (KATP) potassium channels play only a minor role, voltage-gated potassium channels of the Kv1 family play a major role in regulating DA release. The use of Kv subtype-selective blockers confirmed a role for Kv1.2, 1.3 and 1.6, but not Kv1.1, 3.1, 3.2, 3.4 and 4.2. Interestingly, Kv1 blockers also reduced the ability of quinpirole, a D2 receptor agonist, to inhibit evoked DA overflow, thus suggesting that Kv1 channels also regulate presynaptic D2 receptor function. Our work identifies Kv1 potassium channels as key regulators of DA release in the striatum

An Integrative Approach to Learning Processes: Revisiting Substitution of Functions

Based on the assumption that substitution of functions or function transfer is a fundamental principle underlying all conditioning processes, we attempt to produce an account wherein both operant and respondent events are understood in terms of substitution. We contend that, if event interactions are described in a way that accounts for all the stimulus and response events involved in a contingency relation, and further, if we assume symmetry as a property of substitution of functions as excitatory backward conditioning findings seem to suggest, traditional distinctions between operant and respondent conditioning may be rendered unnecessary. We present a reconceptualization of respondent and operant processes and suggest alternatives for empirical research