Summary: Researchers have discovered that dopamine receptors located in the ventral hippocampus are key players in regulating behaviors related to approach and avoidance, deepening our understanding of dopamine beyond its traditional roles in motivation and reward. By examining D1 and D2 receptor-expressing neurons in mice, the study reveals that these receptors influence opposing emotional responses, particularly under stress.
Interestingly, activating D2 receptor neurons was found to lessen fear, which hints at a connection to anxiety and mood management. These insights suggest new possibilities for targeting dopamine pathways in the treatment of conditions like anxiety, depression, and addiction.
Key Facts
- Dopamine in Emotions: D1 and D2 receptors in the ventral hippocampus modulate approach and avoidance behaviors during stress.
- Opposite Effects: D1 and D2 neurons yield contrasting responses, notably as D2 activation leads to reduced fear in mice.
- Therapeutic Potential: This research sheds light on dopamine’s often-overlooked impact on emotional regulation, presenting new ideas for treating mood and anxiety disorders.
Source: Mount Sinai Hospital
Mount Sinai researchers have identified specific functions for two dopamine receptors found on neurons in the brain region that influences approach versus avoidance behaviors.
These receptors may affect anxiety and mood disorders, the origins of which have been somewhat unclear.
The team examined the role of D1 and D2 dopamine receptors in the ventral hippocampus of mice, a part of the brain tied to emotion regulation and reaction to stress.
This work broadens the current understanding of dopamine signaling beyond its established effects on reward and motivation in various brain areas, paving the way for future research on dopamine dysregulation in anxiety and depressive disorders.
The findings were published in the May 7 issue of Nature.
“Healthy emotional processing—especially when balancing decisions regarding approach and avoidance—has long been associated with the hippocampus,” explains Eric J. Nestler, MD, PhD, the study’s senior author and a prominent figure at the Icahn School of Medicine at Mount Sinai. “This is the first comprehensive study of D1 and D2 expressing cells in the ventral hippocampus. We illustrate that dopamine’s role there is more significant than previously understood, especially in decision-making during stressful moments.”
The hippocampus is involved in decision-making under anxiety-provoking circumstances. For instance, when someone must decide whether to pursue food or drink in a threatening environment, approach/avoidance conflicts arise, which can induce fear, confusion, and anxiety.
The Mount Sinai researchers specifically investigated the impact of dopamine signaling within the ventral hippocampus on approach/avoidance behavior in male mice. They found that different neuronal populations expressing D1 and D2 receptors assist in making these decisions.
Notably, these receptors facilitate contrasting approach/avoidance responses and are affected differently by dopamine transmission in that specific brain region.
To the team’s surprise, they discovered that the D1 and D2 receptor-expressing neurons, typically associated with the striatum—an area linked to motor and reward functions—are also significant in the hippocampus.
Additionally, an unexpected finding was that mice with activated D2 cells exhibited significantly reduced fear.
“These discoveries highlight dopamine’s crucial role in the hippocampal circuits, suggesting that its signaling needs to be reassessed in various brain regions, particularly those related to learning, memory, and emotional behaviors,” remarks Dr. Nestler, whose extensive research has focused on understanding the molecular foundations of addiction and depression.
“This work further connects dopamine dysregulation to anxiety and mood disorders.”
Dr. Nestler acknowledges the contributions of co-first authors Arthur Godino, PhD, and Marine Salery, PhD, along with the rest of their research team for their innovative approaches in this study.
Looking ahead, Dr. Nestler and his team aim to clarify exactly how the dopamine-hippocampus circuit that influences approach/avoidance may become dysregulated in various stress-related conditions, such as anxiety and major depressive disorders—where avoidance often increases—as well as in drug addiction, where individuals continue to seek drugs despite adverse effects.
“By elucidating the neuromodulatory circuits involved in these disorders,” states Dr. Nestler, “we are making essential progress towards addressing a major cause of disability worldwide.”
Funding: This research was financed by grants from the National Institute on Drug Abuse, National Institute of Mental Health, and Hope for Depression Research Foundation.
About this dopamine and anxiety research news
Original Research: Closed access.
“Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance” by Eric J. Nestler et al. Nature
