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Dopamine Neurons

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Dopamine Neurons The Addicted Brain Presented by Larry Woodruff, M.S. Ed. [email protected] Expert Resources • Bruce Lipton, Ph.D. Cell biologist, former professor at University of Wisconsin School of Medicine Author and speaker • William Lovallo, Ph.D. Professor of psychiatry and behavioral sciences at University of Oklahoma • Jeanette Norden, Ph.D. Professor of cell and developmental biology Vanderbilt University Expert Resources • Richard Restak, M.D. Clinical Professor of Neurology George Washington University School of Medicine and Health Sciences • Robert Sapolsky, Ph.D. Professor of Neurology and Neurosurgery Stanford University • Brian Luke Seaward, Ph.D. Author of many books on stress and holistic health. Founder and CEO of Inspiration Unlimited. Brain Facts • Adult brain contains ~86 billion neurons • Each neuron makes up to 10,000 connections • Adult brain makes up <3% of total body mass, but uses 20-25% of total body energy (6 kcals/billion neurons/day. • In the womb synaptic connections formed at 1million/second • By first month of life a quadrillion connections have formed Brain Facts • The human cortex contains ~16 billion neurons…More neurons than the cortex of any other animal on the planet. • ~Age 25 the Prefrontal cortex finally matures, and we achieve full potential for rational judgment • Women more prone to addiction than men Physiology of the Neural Impulse Neurons Basics of Neural Transmission • Dendrites receive input from other neurons • If the combined excitatory input reaches a threshold level, an electrical impulse is generated by the neuron (at the axon hillock) and it travels down the axon to the axon terminals • At that point the electrical signal releases chemical molecules (neurotransmitters) that flow into the tiny gap between that neuron and other neurons (called the synapse) and bind with specific receptors (special form of protein molecules) on the dendrites of those other neurons. Basics of Neural Transmission • If enough neurotransmitters bind with enough receptors on another neuron, that neuron generates an impulse (called an “action potential”) • And so on • The critical elements in neuron communication in the brain, and throughout the body, are neurotransmitters and receptors Neurotransmitters Neurotransmitters ~ Facts • Each NT can have vastly different functions in different neurons • The neurotransmitter doesn’t change • Different functions are determined by different receptors • There are 16 different subtypes of serotonin receptors, and several types of receptors for most other NT’s Limbic System ~ Reward Pathway Ventral Tegmental Area (VTA) • Receives sensory input, and attaches pleasure feeling/emotion. Heavy concentration of dopamine neurons. • Primary producer of dopamine in the brain, along with substantia nigrae • Heavily influences nucleus accumbens Limbic System ~ Reward Pathway Nucleus Accumbens • Receives dopamine neurons from VTA • This is the primary brain area associated with addiction • Relays pleasure signals to areas of cortex Mid Forebrain Bundle cortex Dopamine Neurons • These are neurons that have dopamine as their neurotransmitter • They can only communicate with other neurons that have specific receptors for dopamine in the cell membrane of their dendrites • REMEMBER….Dopamine neurons in certain areas of the brain (the reward pathway) produce the sensation of pleasure, and are stimulated by all addictive substances Dopamine Connection • The pleasure signals from increased dopamine in the synapses of thousands of neurons in the Nucleus Accumbens and the Ventral Tegmental Area (the pleasure centers of your brain) are transmitted (via dopamine neuron axons) to neurons in the prefrontal cortex • Once the dopamine signals reach the cortex, we become aware of intense pleasure Mid Forebrain Bundle cortex Opium and its Derivatives OPIUM CODEINE MORPHINE THEBAINE Dilaudid Oxymorphine Percodan (oxycodone) Hereoin Etorphine Opiate / Dopamine Connection • Narcotics a.k.a. Opiates act on opiate receptors on brain neurons that have both opiate and dopamine receptors • There is a complex interaction between opiate receptors and dopamine receptors, such that when opiate receptors are stimulated, they facilitate the binding of dopamine to dopamine receptors on the same neuron. • Other types of addictive drugs will directly stimulate dopamine receptors Key Neurotransmitters Endorphins • Means “the morphine within” • Effective pain suppression • Mild euphoria • Implicated in runner’s high Key Neurotransmitters Endorphins • Opiates stimulate the same receptors as endorphins, only more effectively • Taking opiates suppresses the production of endorphins (our natural pain killers) RESULT – • Natural pain suppression is destroyed and is slow to recover • Withdrawal from long term use of opiates is very painful Reticular Formation • Reticular formation sends projections all over brain Reticular Formation Large system with 110 nuclei • Plays a role in controlling heart rate • Contains respiratory center (medulla) • Respiratory center sends nerve fibers down spinal cord to diaphragm and to intercostal muscles and stimulates them to contract causing lungs to fill with air • This can be shut down by central nervous system depressants such as narcotics and alcohol, and is what causes overdose deaths. Cocaine / Dopamine Connection • Cocaine, on the other hand, does not directly increase dopamine release into the synapse. • Instead it binds with reuptake proteins (magenta colored structures on next slide) • Reuptake proteins act like vacuum cleaners sucking the dopamine molecules out of the synapse and recirculating them back into the sending neuron, thereby not allowing dopamine to bind with dopamine receptors on the receiving neuron for very long. Reuptake proteins Dopamine molecules Post Synaptic Receptors Cocaine Molecules blocking reuptake proteins Cocaine / Dopamine Connection • RESULT…. • Cocaine blocks the reuptake of dopamine, so more dopamine stays in the synapse longer • So….dopamine receptors on the receiving neuron get super stimulated • Bottom line…. Cocaine causes a massive increase in dopamine activation….and therefore the sensation of pleasure THC / Dopamine Connection • Compare the areas of the brain affected by opiates to those affected by THC (active ingredient in marijuana) • The next slide illustrates that THC affects even more brain areas than opiates and cocaine • Note the cerebellum….a critical brain area in balance and coordinated movement THC / Dopamine Connection • The interaction with THC, THC receptors, and dopamine receptors is complex • Much like the interaction of opiates, opiate receptors, and dopamine receptors Brain Areas Adversely Affected by Marijuana Pleasure Neurotransmitters Dopamine and addictive substances • Dopamine receptors decrease in number and sensitivity with long term use of psychoactive substances • Decreased sensitivity can become permanent, resulting in permanent decrease in ability to experience pleasure with normal activities Dopamine Pathways • TI system connects hypothalamus to pituitary • ML system= pleasure producer – VTA to NA to frontal cortex • Nigrostriatal = basal ganglia & motor control Motor Cortices Control of Coordinated Movement • The motor cortex is constantly receiving excitatory input from the cerebellum, and inhibitory input from the basal ganglia • Coordinated movement relies on balancing the excitatory and inhibitory messages received by the motor cortex • Alcohol and other CNS depressants impair the cerebellum, and motor cortex. The greater the BAC the greater the impairment. • Result….. uncoordinated movements beyond conscious control Control of Coordinated Movement Basal Ganglia Key Neurotransmitters Dopamine and motor control • Basal Ganglia work with cerebellum for fine motor control • Shortage of dopamine in 2 basal ganglia causes Parkinson’s disease Pleasure Neurotransmitters Norepinephrine • Vastly different functions in different areas of brain and nervous system • Sensation of pleasure in VTA and nucleus accumbens • Produced in Locus Coeruleus from dopamine • Works either with dopamine or separately to create sensation of pleasure Pleasure Neurotransmitters Norepinephrine • Shortage of NE in pleasure pathways implicated, in part, in clinical depression • NE therefore mood enhancer • Depression associated with insufficient serotonin, dopamine, and norepinephrine; serotonin appears to be most significant. • NE also involved in arousal and attention in several brain areas • Also a hormone secreted by adrenals Key Neurotransmitters Serotonin (5HT) • All brain serotonin produced by Raphe Nuclei in reticular formation • Axons project to all areas of brain • 16 types of serotonin receptors in brain • Serotonin’s effects depend on the type of receptor it binds with. Key Neurotransmitters Serotonin • Helps induce sleep • Mood enhancer • Imbalances in thalamus and certain cortical areas create hallucinations …causes can be sleep deprivation, sensory deprivation, fasting, hallucinogens MDMA Effects of MDMA on Serotonin Activity : • MDMA occupies transporter proteins • Prevents the reuptake of serotonin back into the sending neuron Results : • More serotonin in synapse to bind multiple times with receptors on receiving neuron • Multiply this by thousands of neurons at once Key Neurotransmitters Serotonin • Low levels in PFC associated with depression • Below normal levels in OCD • Below normal levels prior to menstruation in women with severe PMS Key Neurotransmitters Serotonin • Ability to elevate serotonin levels rapidly
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