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

Episode 132 Jul 10, 2023 Episode Page ↗
Overview

Dr. Robert Malenka, MD, PhD, discusses neuroplasticity and the brain's reward systems, focusing on dopamine and serotonin. The conversation explores how these systems influence motivation, addiction, social connections, empathy, and autism spectrum disorders.

At a Glance
18 Insights
2h 47m Duration
19 Topics
7 Concepts

Deep Dive Analysis

Dopamine System & Brain's Reward Circuitry

Reward, Arousal, Memory & Contextual Dopamine Modification

Dopamine, Addictive Liability & Route of Administration

Drugs of Abuse, Brain Changes & Individual Addiction Variability

Reinforcement vs. Reward: Wanting vs. Liking

Opioids, Psychostimulants & Dopamine Mechanisms

Overcoming Self-Doubt & Building Confidence in Academia

Understanding Autism Spectrum Disorder Terminology

Pro-Social Interaction, Reward & Oxytocin's Role

Nucleus Accumbens & Behavior Probability

Evolutionary Basis of Reward for Pro-Social Behavior

Social Media & Gambling: Capitalizing on Reward Circuitry

Pain, Social Behavior & Empathy in Animal Models

Empathy Circuitry, Dopamine & Serotonin

Autism Spectrum Disorder, Social Interactions & Empathy Deficits

MDMA, Serotonin & Dopamine: Addiction & Pro-Social Effects

MDMA Pharmacology & Autism Spectrum Disorder Interventions

Serotonin, MDMA & Classic Psychedelics

Psychedelics: Research & Therapeutic Potential with Caution

Brain's Reward Circuitry

This is a neural circuit, primarily involving dopamine neurons in the ventral tegmental area (VTA) projecting to the nucleus accumbens, that signals when something in the environment is important for survival, either reinforcing (good) or dangerous (bad). It evolved to tell our nervous system what behaviors to repeat or avoid.

Addictive Liability

This concept describes the varying degree to which a substance or behavior can lead to addiction. It is generally correlated with how much dopamine is released in the nucleus accumbens and the kinetics (how rapidly) that dopamine is released, with faster and larger releases typically indicating higher addictive liability.

Reinforcing vs. Rewarding

Reinforcing refers to a stimulus that increases the probability of a behavior being repeated, regardless of subjective feeling. Rewarding implies that the experience actually felt 'good' or enjoyable. A substance can be highly reinforcing (making one want to do it again) without being particularly rewarding (enjoyable).

Wanting vs. Liking

This distinction, coined by Kent Berridge and Terry Robinson, separates the desire for something ('wanting') from the pleasure derived from it ('liking'). A person can 'want' a substance or behavior compulsively without necessarily 'liking' or enjoying it, as seen in some addiction experiences.

Social Buffering of Pain

This phenomenon describes how the presence of others can reduce the experience of pain. In animal models, a mouse in pain can experience analgesia (pain relief) simply by being in the presence of another mouse that has received pain relief, suggesting a social transfer of comfort.

Empathogen

This term refers to a substance that enhances one's capacity for empathy, meaning it increases the ability to understand and share the feelings of another individual. MDMA is often considered an empathogen due to its powerful pro-social effects, though the term is somewhat controversial.

Serotonin Receptors

Serotonin, a powerful neuromodulator, interacts with at least 16 different 'parking spots' or receptor subtypes distributed throughout the brain. Different receptor subtypes, such as serotonin 1b or serotonin 2a, can lead to profoundly different subjective experiences and effects, as seen with MDMA versus classic psychedelics.

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What is dopamine's primary role in the brain?

Dopamine is a major neuromodulator primarily known for its role in the brain's reward circuitry, signaling when a stimulus or experience is important for survival and reinforcing behaviors that lead to it.

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How does context influence the dopamine reward system?

The dopamine reward system is highly plastic and contextually dependent; the same stimulus (e.g., food, a person) can elicit very different dopamine responses depending on current needs, memories, and prior experiences, which modify how the circuitry responds.

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Is the rate of dopamine increase related to a drug's addictive potential?

Yes, the addictive liability of a substance is directly correlated with both how much dopamine is released in the nucleus accumbens and the kinetics (how rapidly) that dopamine is released. Faster, more rapid surges of dopamine tend to increase addictive potential.

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Do drugs of abuse cause lasting changes in brain circuitry?

Yes, drugs of abuse like cocaine, methamphetamine, and opioids cause powerful neuroplastic changes in the connections (synapses) of neurons within the reward circuitry, including dopamine neurons and those in the nucleus accumbens, which can last for days or weeks.

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Why do some individuals become addicted while others do not, even with exposure to the same substance?

Individual variability in addiction susceptibility is a complex combination of underlying genetics, the environment in which a person grew up, and their current life circumstances, including the availability of other reinforcing stimuli or healthy outlets.

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How do opioids and psychostimulants (like cocaine) differ in their impact on the dopamine system?

Both opioids and psychostimulants ultimately cause a massive release of dopamine in the nucleus accumbens, but they do so via different molecular mechanisms. Psychostimulants primarily block the reuptake of dopamine and can cause its reverse transport, while opioids indirectly increase the activity of dopamine neurons themselves.

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How should we refer to autism spectrum disorder?

Autism spectrum disorder is a heterogeneous condition, and it's best to be sensitive to individual preferences. While some individuals with severe impairments may be described as having a disorder requiring help, high-functioning individuals may prefer to be seen as having a different style of living and interaction rather than an illness.

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Is social interaction rewarded through the dopamine system?

Yes, positive pro-social interactions are highly reinforcing and involve the dopamine system, with dopamine being released in the nucleus accumbens during these interactions. Oxytocin and serotonin also play prominent roles in mediating social reward.

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How does social media capitalize on the brain's reward mechanisms?

Social media platforms capitalize on hardwired, primitive neurobiological mechanisms that evolved for physical interpersonal interactions, triggering the release of dopamine, serotonin, and oxytocin through recognition, messages, and other forms of social feedback, creating a compulsive, addictive quality for many users.

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Does autism involve a lack of empathy or altered social reward?

Studies in human beings and mouse models suggest that the reinforcing component of social interaction can be much less or lacking in some individuals with autism spectrum disorder. It is also likely that some individuals with autism may lack some of the neuromechanisms that allow for empathy.

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What is the role of serotonin in the pro-social effects of MDMA?

Research suggests that the positive, pro-social, and potentially empathogenic effects of MDMA are more likely to be mediated by its interactions with the serotonin system, particularly through serotonin release in the nucleus accumbens, rather than solely by dopamine.

1. Prioritize Empathy & Compassion

Recognize that empathy and compassion are crucial for human survival; strive to understand that another person’s suffering is akin to your own, regardless of differences in appearance or belief systems.

2. Prevent Addiction: Never Start

It is impossible to become addicted to a substance if you have never used it, so avoiding initial use eliminates the risk of developing an addiction.

3. Cultivate Healthy Rewards

Actively seek out healthy ways to activate your brain’s reward circuitry, such as exercise, to gain satisfaction and reinforce positive behaviors.

4. Reward Abstinence Behaviors

In recovery, actively create rewards around abstaining from addictive substances or behaviors, cognitively teaching yourself to find satisfaction and liking in sobriety.

5. Recognize Genetic Addiction Risk

Be aware that there is a genetic component to addiction, particularly with substances like alcohol, and consider family history when assessing personal risk.

6. Assess Addiction Risk

Before trying a substance, especially as a young person, assess the inherent risk of developing an addiction, as even a single exposure can cause lasting changes in brain circuitry.

7. Dopamine Signals Importance

Understand that the dopamine system signals not only rewarding experiences but also painful or aversive stimuli, linking both to arousal and memory systems to help you remember important environmental events for survival.

8. Ensure Proper Hydration & Electrolytes

Maintain proper hydration and adequate electrolyte intake (sodium, magnesium, potassium) for optimal brain and body function, as even slight dehydration can diminish cognitive and physical performance.

9. Huberman’s Hydration Protocol

Dissolve one packet of Element in 16-32 ounces of water first thing in the morning and during any physical exercise to ensure proper hydration and electrolyte balance.

10. Restore Energy with NSDR

Engage in yoga nidra or non-sleep deep rest (NSDR) sessions, even for just 10 minutes, to greatly restore levels of cognitive and physical energy.

11. Utilize Meditation Apps

Explore meditation apps like Waking Up, which offer diverse programs including mindfulness, yoga nidra, and non-sleep deep rest (NSDR) protocols, to place the brain and body into different states.

12. Social Buffering of Pain

Engage socially when experiencing pain, as social interaction can provide relief and reduce focus on discomfort, a phenomenon known as social buffering of pain.

13. Leverage Non-Verbal Social Cues

Be aware that non-verbal social cues, such as touch or even a nod, can powerfully impact well-being, provide comfort, and offer a sense of connection, especially during times of pain or struggle.

14. Work For Yourself Mindset

Even when working with mentors, adopt a mindset of working for yourself and viewing them as colleagues from whom you can learn, fostering a sense of equality and ownership over your work.

15. Build Confidence Gradually

Build confidence gradually over time by engaging in challenging work, developing a ’tougher and thicker skin’ to argue and defend your ideas, and realizing it’s okay to voice your opinions and beliefs.

16. Mind Social Media’s Addictive Nature

Recognize that social media and digital communication capitalize on primitive reward mechanisms, leading to compulsive behaviors similar to addiction due to immediate feedback and the desire for recognition.

17. Beware Intermittent Rewards

Understand that gambling capitalizes on the brain’s reward circuitry through intermittent rewards, which are very powerful and designed to keep individuals coming back despite potential losses.

18. Approach Psychedelics Cautiously

Approach the use of psychedelics and MDMA with caution, recognizing they are not miracle cures and can lead to very bad experiences, emphasizing the need for rigorous, sophisticated, and ethical scientific study.

I hate this, and I can't wait to do it again.

Dr. Robert Malenka

You can't become addicted to a substance if you've never used it, by definition.

Dr. Robert Malenka

The most successful scientists I know are pretty passionate and pretty intense about what they're working on and driven.

Dr. Robert Malenka

What is more important for the survival of the human species than empathy and compassion?

Dr. Robert Malenka

The brain's unfortunately complicated, you know, we like, we like it's tractable, we like to come up with general hypotheses and principles, but sometimes the devil's in the details and we really need to probe deeper.

Dr. Robert Malenka

I do worry that if some people take these substances and bad things happen, it will slow down the excitement that's currently happening and it will make it more difficult for serious human subjects researchers, preclinical researchers to study these substances in the way they deserve to be studied.

Dr. Robert Malenka
Several days to several weeks
Duration of changes in neural connections from a single drug exposure (rodent models) For drugs like cocaine or morphine, changes in connections onto dopamine neurons and nucleus accumbens neurons can last this long, though not permanent.
4 to 20 hours
Duration of pain manifestation in bystander mouse after exposure to mouse in pain A mouse exposed to another mouse in pain for one hour will show pain behaviors for this duration.
70% serotonin, 30% dopamine (or 80% serotonin, 20% dopamine)
Approximate ratio of MDMA's influence on serotonin vs. dopamine systems MDMA influences the serotonin system more than the dopamine system due to its higher affinity for serotonin transporters.
16
Number of different serotonin receptor subtypes These different receptor subtypes are distributed in various brain areas and offer possibilities for targeted therapeutic agents.
42 million dollars
Funding from opioid lawsuit settlement for ibogaine study in Kentucky From the Purdue Pharmaceuticals settlement, allocated for research into ibogaine.