Researchers have uncovered new insights into how fasting alters dopamine signaling in the brain’s reward circuitry.
Their findings, published in the Journal of Neurophysiology, suggest that fasted mice exhibit enhanced dopamine release in the ventral tegmental area (VTA) of the brain compared to fed mice.
This may help explain fasting’s impact on motivation and reward-seeking behaviors.
Key Facts:
- Mice fasted for 24 hours showed increased dopamine release in the VTA compared to fed mice.
- Fasted mice had larger dopamine responses to initial action potentials and sustained release during burst firing.
- The dopamine increase appears to be due to greater release probability, not changes in dopamine receptors.
- Fasting may lower tonic dopamine levels but increase phasic bursts during salient events.
- These VTA changes likely contribute to fasting’s effects on motivation and reward processing.
Source: J Neurophysiology
The Ventral Tegmental Area: Center of Motivation & Reward
The VTA is located deep in the brain and contains dopamine neurons that project to areas involved in motivation, reward valuation, and action selection.
VTA dopamine signaling encodes reward prediction errors – whether something is better or worse than expected.
Phasic bursts of dopamine neurons reinforce rewarding behaviors, while dips below baseline dopamine levels encode perceived losses or punishments.
Through these teaching signals, VTA dopamine neurons shape motivation and goal-directed behaviors.
Unsurprisingly, altered VTA dopamine transmission underlies disorders involving reward processing like addiction and obesity.
Because of the VTA’s central role in motivation and reward, scientists are keenly interested in how natural modulators like fasting affect its dopamine signaling.
Probing Dopamine Release in Fasted vs Fed Mice
The researchers performed experiments probing two types of dopamine release from VTA neurons:
- Axonal release to downstream targets like the nucleus accumbens.
- Local somatodendritic release within the VTA that inhibits neighboring dopamine neurons through D2 autoreceptors.
To compare dopamine release between 24-hour fasted mice and normally fed control mice, the researchers electrically stimulated VTA dopamine neurons and measured resulting inhibitory postsynaptic currents mediated by D2 autoreceptors (D2R-IPSCs).
Fasted Mice Show Enhanced Dopamine Release in Response to Stimulation
The key finding was that fasted mice exhibited increased D2R-IPSCs compared to fed mice, indicative of greater somatodendritic dopamine release.
Specifically, fasted mice showed:
- Larger contributions of initial stimuli to overall dopamine responses
- Increased dopamine release sustainability during burst firing
- Heightened calcium sensitivity – IPSCs decreased more in low calcium
- Reduced amplification of release by forskolin – already near maximal levels
The researchers performed additional experiments to confirm the effects originate presynaptically from increased vesicular dopamine release, not postsynaptic D2 receptor changes.
Putting the Pieces Together – Possible Mechanisms
Though contrary to reduced dopamine levels seen in target regions during food restriction, the VTA dopamine increase aligns with previous observations that restricted animals show enhanced motivation and reward responses.
The researchers propose possible explanations for this discrepancy:
- Increased somatodendritic dopamine may lower tonic dopamine levels but facilitate salient phasic bursting
- Local VTA inhibition may synchronize populations of dopamine neurons for coordinated responses to rewards
While the exact mechanisms relating VTA dopamine changes to motivation and behavior require further study, these findings advance our understanding of how fasting acts on the brain’s reward circuitry.
Potential Implications and Future Directions
Beyond providing new neurobiological insights into fasting, these results have interesting implications:
- The VTA dopamine increase may underlie fasting’s variable effects on drug reward and addiction susceptibility
- Similar mechanisms could contribute to altered motivation and dopamine function in obesity
- Therapeutically targeting VTA dopamine could mitigate fasting’s effects in disorders involving altered motivation and compulsive behaviors
Future research can build on these findings by:
- Correlating VTA dopamine changes to behavioral effects of fasting
- Elucidating intracellular signaling pathways mediating the enhanced dopamine release
- Exploring how longer fasting durations impact VTA dopamine signaling
- Investigating effects of intermittent fasting and caloric restriction on VTA function
In summary, this research elucidates how dopamine neurotransmission in the brain’s appetitive center is shaped by the ubiquitous yet understudied condition of fasting.
Beyond revealing new biology, these discoveries pave the way for leveraging neurochemical understanding to improve treatments for compulsive behaviors related to reward and motivation.
References
- Study: Acute fasting increases somatodendritic dopamine release in teh ventral tegmental area
- Author: Aaron G. Roseberry (2015)
