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Huberman Lab
Dr. Robert Malenka: How Your Brain’s Reward Circuits Drive Your Choices
Jul 10, 2023
02:47:29
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Quick takeaways
- Different addictive substances impact the dopamine reward circuitry in distinct ways, leading to varying subjective experiences.
- Individual susceptibility to addiction is influenced by genetic factors, environmental factors, and available rewards.
- Addiction treatment focuses on shifting the focus from wanting the addictive substance towards finding reward in healthy alternatives.
- Autism spectrum disorder may be associated with altered reward processing and deficits in social reward.
- Neuromodulatory systems, particularly serotonin, may hold promise for enhancing empathy and social behaviors.
Deep dives
The Influence of Dopamine in Addiction
Different drugs, such as cocaine, opioids, and methamphetamine, impact the dopamine reward circuitry in the brain, leading to addictive behaviors. Cocaine and methamphetamine directly affect the release and reuptake of dopamine, causing a rapid and powerful surge in the brain's reward circuitry. Opioids primarily act on the dopamine neurons themselves, triggering an increased release of dopamine. The addictive properties of these substances are influenced by the amount of dopamine released as well as the kinetics of release. The subjective experiences and effects of these substances can vary widely, with opioids offering a more sedative experience and psychostimulants inducing increased arousal and stimulation. The development of addiction depends on a combination of genetic predisposition, environmental factors, and individual susceptibility.
Neuroplasticity and Addiction
Addictive substances, including drugs like cocaine and opioids, can cause changes in the synaptic connections within the dopamine reward circuitry, leading to long-lasting modifications in the brain's response to the drug. These changes in the reward circuitry are a form of neuroplasticity, which allows the brain to adapt and change in response to experiences. Single exposures to drugs can produce temporary changes, while repeated exposure can lead to stronger and longer-lasting plasticity. However, individual susceptibility to addiction varies, and factors such as genetics, environment, and available rewards can influence the development and severity of addiction.
Variations in Addictive Experiences
Different addictive substances and behaviors impact the dopamine reward circuitry in unique ways, resulting in distinct subjective experiences. For instance, cocaine and methamphetamine have a rapid onset and short-lived effects, creating feelings of stimulation and increased arousal. Opioids, on the other hand, induce sedation and dream-like experiences. Additionally, individual responses to these substances can vary due to factors such as genetic predisposition, previous exposure, and environmental context. Subjective experiences can range from finding a substance highly enjoyable and reinforcing to feeling aversive or indifferent towards it.
Distinguishing Between Wanting and Liking
In addictive behaviors, it is important to distinguish between 'wanting' and 'liking.' Wanting refers to the drive and compulsion to engage in a behavior or consume a substance, while liking refers to the actual enjoyment or pleasure derived from it. Addiction treatment programs often aim to shift the focus from wanting the addictive substance or behavior towards finding satisfaction and reward in healthy alternatives. The neurobiological mechanisms underlying wanting and liking are complex and involve a combination of neural circuits, neurotransmitters, and the interaction between genetic and environmental factors.
Empathy and Reward Circuitry in Autism
Research suggests that individuals with autism spectrum disorder may have differences in brain wiring that contribute to altered reward processing, potentially leading to reduced social reward. Imaging studies have shown that social interactions may be less reinforcing for individuals with autism spectrum disorder. However, the experience of empathy in autism is complex and varies among individuals. Mouse models of autism spectrum disorder also exhibit deficits in social interactions and empathy-like behaviors. These deficits can be improved with manipulations of neuromodulatory systems, such as the serotonin system, and drugs like MDMA have shown promising effects in enhancing social behavior and empathy in autism spectrum disorder mouse models.
Investigating Empathy and Social Behaviors in Mice
Experimental assays in mice are being developed to study empathy and social behaviors. These assays include the social transfer of pain, where a mouse in pain can communicate its pain state to another mouse, and the social transfer of analgesia, where a mouse experiencing pain relief can alleviate the pain of another mouse. These behavioral models provide insights into the neurobiology of empathy and prosocial behaviors. The anterior cingulate cortex and its connections to the nucleus accumbens have been implicated in empathic behaviors, and the influence of neuromodulators like serotonin and dopamine on these connections are areas of active research.
Understanding Empathy and its Evolutionary Significance
Empathy is believed to have evolutionary significance in promoting social cohesion, cooperation, and survival. The ability to understand and share the emotions of others, and to provide support and assistance, allows for the development of social bonds and increased chances of reproductive success. Neurobiological mechanisms involved in empathy are being studied in both humans and animal models, with a focus on areas such as the anterior cingulate cortex and the nucleus accumbens. Understanding the neurobiology of empathy may have implications for various conditions, including autism spectrum disorder, where altered social reward processing and empathy deficits are often observed.
Role of Neuromodulators in Empathy and Reward Processing
Neuromodulators like serotonin and dopamine play crucial roles in empathy and reward processing. The release of serotonin in the nucleus accumbens has been associated with empathy and positive social interactions. Mouse models and studies with drugs like MDMA (ecstasy) have shown that serotonin released in the nucleus accumbens is involved in the prosocial effects of the drug. These findings suggest that manipulating neuromodulatory systems, particularly serotonin, may hold promise for enhancing empathy and social behaviors in various contexts, including autism spectrum disorder.
The Potential Therapeutic Uses of Oxytocin in Autism
There has been excitement about the potential of using oxytocin nasal sprays to improve social interactions in individuals with autism. However, there is currently no evidence to support the idea that increasing oxytocin in children or adults with autism makes them more social or desire more social connections. Clinical trials with intranasal oxytocin have been disappointing, but researchers believe that there may still be potential therapeutic uses for oxytocin or related agents. It is possible that different methods of administration or modified versions of oxytocin could be more beneficial. Some promising research is also being conducted on a related neuropeptide called vasopressin.
Understanding the Effects of MDMA on the Brain
MDMA affects the brain's serotonin and dopamine systems, causing increased release of these neurotransmitters and leading to its unique subjective effects. Unlike cocaine or methamphetamines, MDMA primarily influences the serotonin system, although it also affects the dopamine system to a lesser extent. This distinction may explain why MDMA has a different qualitative experience compared to other stimulant drugs. The serotonin-dominant effects of MDMA are believed to contribute to its positive pro-social and empathogenic effects, while its addictive liability and reinforcing qualities are likely mediated by its actions on the dopamine system. Ongoing research aims to further understand these mechanisms and explore the potential therapeutic benefits of MDMA, particularly in the treatment of post-traumatic stress disorder.
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3min
54.
Neuroplasticity, Reward Systems, Social Connection and Empathy With Dr. Robert Malenka
2min
In this episode, my guest is Robert Malenka, MD, PhD, a professor of psychiatry and behavioral sciences at Stanford School of Medicine who has made numerous seminal discoveries of how the brain changes (neuroplasticity) in response to learning and in response to rewarding and reinforcing experiences. We discuss the brain’s several reward systems involving dopamine and serotonin and how these motivate us to seek out specific behaviors and substances. We discuss how these reward systems are modified based on context and our memories, and how they can be hijacked toward maladaptive drug seeking in addiction. We also explore how reward systems influence social connections, oxytocin and empathy and how that applies to our understanding of autism spectrum disorders. This episode should be of interest to those interested in neuroplasticity, social bonding, addiction, autism, learning and motivation.
For show notes, including referenced articles and additional resources, please visit hubermanlab.com.
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Timestamps
(00:00:00) Dr. Robert Malenka
(00:02:53) Sponsors: LMNT & Waking Up
(00:05:21) Dopamine & Reward Circuitry
(00:11:31) Reward, Arousal, Memory & Dopamine
(00:17:34) Context, Cues & Dopamine Modification
(00:25:38) Memory & Reward Scaling
(00:30:50) Dopamine, “Addictive Liability” & Route of Administration
(00:39:25) Sponsor: AG1 (Athletic Greens)
(00:40:40) Drugs of Abuse & Brain Changes; Addiction & Individual Variability
(00:50:51) Reinforcement vs. Reward, Wanting vs. Liking
(00:57:500 Opioids, Psychostimulants & Dopamine
(01:04:51) Self-Doubt, Confidence & Career
(01:12:40) Autism Spectrum Disorder
(01:19:29) Pro-Social Interaction & Reward; Oxytocin, Serotonin & Dopamine
(01:30:30) Nucleus Accumbens & Behavior Probability
(01:38:28) Reward for Pro-Social Behavior
(01:43:13) Social Media & “Addictive Liability”; Gambling
(01:52:17) Pain, Social Behavior & Empathy
(02:02:19) Empathy Circuitry, Dopamine & Serotonin
(02:10:07) Autism Spectrum Disorder & Social Interactions, Empathy
(02:17:23) MDMA, Serotonin & Dopamine; Addiction & Pro-Social Effects
(02:28:13) Autism Spectrum Disorder, Social Behavior, MDMA & Pharmacology
(02:37:18) Serotonin, MDMA & Psychedelics
(02:40:16) Psychedelics: Research & Therapeutic Potential
(02:47:57) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter
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