July 10, 2023 • 2hr 47min

Dr. Robert Malenka: How Your Brain’s Reward Circuits Drive Your Choices

Huberman Lab

In this episode, Dr. Andrew Huberman interviews Dr. Robert Malenka, a professor of psychiatry and behavioral sciences at Stanford University School of Medicine. Dr. Malenka is a world-renowned expert on the neurobiology of reward, addiction, and social behaviors. The discussion covers a wide range of topics related to how the brain's reward systems drive our choices and behaviors.

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Key Takeaways

The dopamine reward system evolved to reinforce behaviors important for survival, like eating high-calorie foods and social bonding. However, this system can be hijacked by drugs of abuse and other stimuli.
Dopamine release in the nucleus accumbens signals that something important is happening and should be remembered. It's closely tied to arousal and memory systems.
The reward system is highly context-dependent and plastic. The same stimulus can be rewarding or aversive depending on context and past experiences.
Drugs of abuse cause massive dopamine release and long-lasting changes in reward circuitry. However, not everyone who tries drugs becomes addicted.
Social interactions are highly rewarding and involve dopamine, serotonin, and oxytocin systems working together in complex ways.
Some individuals with autism spectrum disorder may have deficits in finding social interactions rewarding. Targeting the serotonin system may have therapeutic potential.
MDMA (ecstasy) has powerful prosocial effects, likely mediated more by serotonin than dopamine. It is being studied as a potential therapy for PTSD and autism.
Psychedelic drugs like psilocybin and LSD work primarily through serotonin systems and can produce mystical-type experiences. They are being studied for depression and other conditions.
While psychedelic drugs show therapeutic promise, caution is needed. They are not miracle cures and can potentially cause harm in some individuals.

Introduction

In this episode, Dr. Andrew Huberman interviews Dr. Robert Malenka, a professor of psychiatry and behavioral sciences at Stanford University School of Medicine. Dr. Malenka is a world-renowned expert on the neurobiology of reward, addiction, and social behaviors. The discussion covers a wide range of topics related to how the brain's reward systems drive our choices and behaviors.

Topics Discussed

Dopamine and the Reward System (5:21)

Dr. Malenka explains that dopamine is a key neurotransmitter in the brain's reward circuitry. The main dopamine neurons involved in reward are located in the ventral tegmental area (VTA) and project to the nucleus accumbens.

Dopamine release signals that something important is happening in the environment
This system evolved to reinforce behaviors important for survival, like eating high-calorie foods
Dopamine release is closely tied to arousal and memory systems
"What evolved is a mechanism to tell our nervous systems and tell our brains, this feels pretty good. I should repeat the behavior that leads to that rewarding experience." - Dr. Robert Malenka

Context and Plasticity of Reward (17:34)

The reward system is highly context-dependent and plastic, meaning it can change based on experiences. Dr. Malenka gives the example of Thanksgiving dinner:

In the morning, the smells of cooking food are highly appetitive and rewarding
By evening, those same smells may be aversive after overeating
This rapid change in response to the same stimuli is due to plasticity in the reward system
Past experiences and context strongly influence how rewarding a stimulus is

Addiction and Drugs of Abuse (30:50)

Dr. Malenka discusses how drugs of abuse impact the dopamine system:

Drugs like cocaine and opioids cause massive dopamine release in the nucleus accumbens
The speed of dopamine increase correlates with addictive potential
Route of administration (e.g. smoking vs snorting) affects how quickly dopamine increases
Drugs cause long-lasting changes in reward circuitry connections
Not everyone who tries drugs becomes addicted - genetics and environment play a role

Social Reward and Empathy (1:19:29)

The discussion turns to how social interactions activate reward systems:

Prosocial interactions are highly rewarding for most people
This likely evolved to promote behaviors that increase survival, like group bonding
Social reward involves dopamine, serotonin, and oxytocin systems working together
Dr. Malenka's lab studies "behavioral antecedents of empathy" in mice
The anterior cingulate cortex and nucleus accumbens are involved in empathy-like behaviors in mice

Autism Spectrum Disorder (2:10:07)

They discuss how reward systems may be altered in autism spectrum disorder (ASD):

Some individuals with ASD may find social interactions less rewarding
There is evidence of serotonin system dysfunction in ASD
Mouse models of ASD show deficits in social behaviors that can be rescued by manipulating serotonin
Clinical trials of oxytocin for ASD have been mostly disappointing so far
Targeting specific serotonin receptors may have therapeutic potential for ASD

MDMA and Serotonin (2:17:23)

Dr. Malenka discusses his lab's research on MDMA (ecstasy):

MDMA causes release of both dopamine and serotonin, but affects serotonin more
The prosocial effects of MDMA appear to be mediated more by serotonin than dopamine
MDMA is being studied as a potential therapy for PTSD and social anxiety in autism
Different forms of MDMA may have different ratios of dopamine/serotonin effects
"How does a drug that has molecular targets in the dopamine neuromodulatory system, in the serotonin neuromodulatory system have such a powerful effect, which is relatively specific on social interactions? ... There's something really important from that phenomenological observation in the human experiences that we can learn from." - Dr. Robert Malenka

Psychedelics Research (2:40:16)

The conversation concludes with a discussion of psychedelic drug research:

Classic psychedelics like psilocybin and LSD work primarily through serotonin 2A receptors
They can produce mystical-type experiences and are being studied for depression and other conditions
Dr. Malenka is excited but cautious about psychedelic research
He emphasizes the need for rigorous, ethical studies
Psychedelics are not miracle cures and can potentially cause harm in some individuals
Careful screening of participants is important in clinical trials

Conclusion

This wide-ranging discussion with Dr. Robert Malenka provides deep insights into how the brain's reward systems shape our behaviors and choices. From the basic neurobiology of dopamine to cutting-edge research on psychedelics, the conversation highlights both the complexity of these systems and their importance for understanding human behavior. Dr. Malenka's work on social reward and empathy opens up exciting possibilities for new treatments for conditions like autism spectrum disorder. At the same time, his measured perspective on psychedelic research emphasizes the need for careful, ethical studies as this field moves forward. Overall, this episode underscores the profound impact that reward circuitry has on our lives and the potential for leveraging this knowledge to improve mental health treatments.