On the role of subsecond dopamine release in conditioned avoidance

Abstract

Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response. Current neuroscientific advances are providing new perspectives into this historical literature. Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior. We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event. The latter observation is inconsistent with the second component of the two-factor theory of avoidance and; therefore, led us propose a new theoretical explanation of conditioned avoidance: (1) fear is initially conditioned to the warning signal and dopamine computes this fear association as a decrease in release, (2) the warning signal, now capable of producing a negative emotional state, suppresses dopamine release and behavior, (3) over repeated trials the warning signal becomes associated with safety rather than fear; dopaminergic neurons already compute safety as an increase in release and begin to encode the warning signal as the earliest predictor of safety (4) the warning signal now promotes conditioned avoidance via dopaminergic modulation of the brain's incentive-motivational circuitry.

Keywords: conditioned avoidance; dopamine; fear conditioning; nucleus accumbens; voltammetry.

Figure 1

Illustration of the first conditioned avoidance (initially described as a conditioned reflex) experiment conducted in America by John B Watson. Electrodes were placed under the hand and finger of a human subject. An auditory stimulus was presented prior to the delivery of electrical shock. A recording device allowed for the detection of finger movements evoked by the shock and the preceding auditory stimulus. Within a few trials, finger withdrawal began to occur to the auditory stimulus. The conditioned finger withdrawal broke the circuit between the two electrodes, which was necessary for the delivery of electric shock. Originally published in Watson (1916).

Figure 2

The role of subsecond dopamine release during conditioned avoidance. (A) Changes in subsecond dopamine release observed in different response types observed in a single session. Representative color plots (left) and dopamine concentration traces (right) show avoidance (top), one-footshock escape (middle), and two-footshock escape (bottom) responses. Left, the y-axis represents the scan potential (Epp, V) applied to the electrode, the x-axis represents time, and the z-axis represents current. Inspection of the color plot allows for the identification of dopamine over time. Dopamine can be identified in the color plot by assessing for changes in current at the oxidation (+0.6V) and reduction (−0.2V) potentials for dopamine. Right, representative dopamine concentration traces plotted as a function of time with the inset showing the cyclic voltammograms for dopamine. Arrows indicate lever responses, lightning bolts indicate footshocks, trumpets indicate safety periods, levers + lights indicate warning signals. (B,C) Mean ± SEM dopamine concentration traces from all avoidance and escape responses. Maximal warning signal duration is representative by the light gray fill, subsequent safety periods are represented by the dark gray fill. (D) Maximal dopamine concentration evoked by warning signal presentation predicts conditioned avoidance. Originally published in Oleson et al. (2012).

Figure 3

Fear-conditioned stimuli freeze behavior and subsecond dopamine release events. (A,B) An otherwise neutral stimulus (trumpet) previously conditioned to inescapable footshock (lightning bolt) produces freezing behavior that extinguishes across repeated trials of conditioned stimulus (CS) presentation on fear-memory retrieval day. (C) Representative color plot (left) and corresponding dopamine concentration trace (right) show a CS-induced decrease in dopamine release. Gray represents CS duration. (D) Mean ± SEM dopamine concentration trace during presentations of the fear-conditioned CS. Originally published in Oleson et al. (2012).