The Effects of Corticotropin-Releasing Factor on Dopamine Release: Implications for Reward and Effort
Take home messages:
- Corticotropin releasing factor (CRF) acts in the ventral tegmental area (VTA), a primary source of dopaminergic neurons and an integral part of the mesolimbic reward pathway, to regulate dopamine (DA) neurotransmission.
- A large reward (large reward magnitude) will enhance motivated behavior.
- A large reward magnitude also enhances DA release in response to cues and rewards.
- CRF, a hormone and neurotransmitter implicated in the stress response (HPA axis), in the VTA will attenuate motivated behavior in a dose-dependent manner and this effect is not due to motor suppression.
- CRF in the VTA attenuates phasic DA release (burst DA release as opposed to a more gradual release) specifically to rewards, not the cues related to the rewards.
- Satiety (being full) will reduce motivated behavior (in this case the reward was food pellets) as well as DA release to rewards (but not cues).
Author Abstract (Phillips, et. al) : Phasic dopamine release during reward and effort manipulations: Effects of corticotropin release factor.
The effort an individual is willing to exert to obtain a reward is dependent upon one’s motivational state as well as the value of the reward. Contemporary theories of dopamine function suggest that dopamine release, particularly in the striatum, is involved with enabling high-effort behaviors. Motivated behaviors can be influenced by stressful stimuli and stress-released neuropeptides such as corticotropin-releasing factor (CRF). The behavioral effects of stress on motivation could involve the midbrain dopamine system as (i) stress increases dopamine levels, (ii) CRF is released into the midbrain during stress, and (iii) CRF increases the firing rate and potentiates glutamate receptor current in dopamine neurons. Thus, we hypothesized that CRF in the VTA will elevate phasic dopamine release and increase the effort exerted to obtain a reward. However, before addressing this pharmacological question it was important to first determine how natural manipulations of motivational state and reward magnitude influence phasic dopamine release during high-effort behaviors.
We utilized fast-scan cyclic voltammetry to examine phasic striatal dopamine release to rewards and reward-predictive cues in rats performing an operant task under a progressive ratio (PR) reinforcement schedule for natural reinforcers. In separate sessions, we assessed behavior and dopamine release in rats under different motivational states (food-deprived or free-fed) or working for rewards of different magnitudes. The cumulative number of rewards earned scaled with the reward size in a given PR session. Interestingly, we found that motivational state and reward size robustly scaled reward-evoked dopamine release, while cue-evoked dopamine release was less sensitive to these manipulations. After establishing the effect of natural manipulations, we next examined how CRF injections into the midbrain affected behavior and dopamine release during PR sessions. Contrary to our hypothesis, CRF injected into the midbrain lowered the breakpoint in PR sessions. Furthermore, CRF injections attenuated reward-evoked dopamine release but did not affect cue-evoked dopamine release. Together, these results suggest that CRF modulates motivated behavior by affecting either dopamine neurons responsive to reward delivery and/or inputs to the midbrain representing the delivery of rewards.
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