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Dopamine Links to Parkinson’s disease, Schizophrenia and narcotics Dopamine • Dopamine is a neurotransmitter in its own right as well as being a precursor for adrenaline and noradrenaline. Low levels of dopamine are associated with Parkinson’s disease, which is characterised by tremor and uncontrolled movements. It is treated with L-dopa (laevodopa), which is a precursor for dopamine. In contrast, high levels of dopamine are linked to schizophrenia, increased arousal, reduced inhibition and increased creativity. • Q Suggest why treatment with L-dopa might reduce tremor in Parkinson’s disease patients. • As with any neurotransmitter, there must be receptors for it to bind to. There are five different dopamine receptors, identified as DRD1 through to DRD5 (dopamine receptor D1 to D5). One of them, DRD4 has many variants and some of these are linked to specific conditions such as: • ADHD or attention deficit hyperactivity disorder • addictive/risk-taking activity • schizophrenia Dopamine and Parkinson’s • Among other areas Dopamine works in the brain’s movement and motor system. • If this level of dopamine decreases below the “normal range” we begin to experience more motor and grossmovement problems. • Very low levels of Dopamine in the motor areas of the brain are known to produce Parkinson’s Disease. Symptoms of Parkinson’s • • • • • • • • • • • • Muscle rigidity, aches and stiffness Stooped/unstable posture Loss of balance and coordination Gait (walking pattern) disturbance Slow movements and difficulty with voluntary movements Small-step gait/walking Tremors and shaking Fixed, mask-like facial expression Slow, monotone speech Impairment of fine-motor skills Falling when walking Impairment in cognitive/intellectual ability Basically, fewer or weakened/ damaged neurones release less dopamine leading to fewer action potentials in the vast number of neurones reliant upon this neurotransmitter Other examples of dopamine agonists include: Requip, Permax Dopamine and ADHD • Dopamine in the thinking areas of the brain could be considered the neurotransmitter of focus and attending • Low levels impair our ability to focus on our environment or to “lock on” to tasks, activities, or conversations • Low levels of Dopamine make concentration and focus very difficult with low levels also associated with Attention-Deficit Hyperactivity Disorder (ADHD) TREATMENT: Attention deficit hyperactivity disorder • ADHD patients have lower levels of dopamine receptors and transporters in the regions of the brain that are responsible for motivation and reward. • It seems strange to treat people with hyperactivity with a stimulant, but this is exactly what happens. • ADHD is treated with the stimulant Ritalin (methylphenidate) which increases the amount of dopamine in the brain as it compensates for the deficient reward system and suppresses the background firing of neurones, so decreasing the effect of distracters. • If Dopamine levels in the brain begin to raise, we become excited/energized, then suspicious and paranoid, then finally hyper-stimulated by our environment. Can you guess which drug/s • With low levels of Dopamine, we can’t focus stimulate dopamine production? while with high levels of Dopamine our focus becomes narrowed and intense to the point of focusing on everything in our environment as though it were directly related to our situation. You can clearly see the comparatively low level of activity due to low dopamine levels Drugs and the brain • High levels of Dopamine are found in Schizophrenia, drug intoxication, and other psychotic conditions where the ability to distinguish the inner world from the real world is impaired. • Nicotine (relatively low levels stimulated) • Cocaine • Speed (amphetamines) Treatment • Dopamine blockers (e.g. Domperidone) are used • They bind to the dopamine receptors on the post synaptic membrane preventing dopamine binding • This prevents an action potential The third row shows the same addict’s brain after 100 days without any cocaine. We can see a little more yellow, so there is some improvement more brain activity - at this point. But the addict’s brain is still not back to a normal level of functioning... more than 3 months later. Scientists are concerned that there may areasrow in the brain Thebe middle shows a cocaine addict’s brain after 10 days In never this image, the level of brain function isto indicated in that fully recover This PET scan shows us that once addicted a drug like without any cocaine use at all. What is happening here? yellow. The top rowisshows a normal-functioning brain from drug abuse and cocaine, the brain affected for a long, long time. In Less yellow means less normal activity occurring in the without drugs.once Youaddicted, can see a the lot of brain activity.changed. In other addiction. other words, brain is literally brain - even after the cocaine abuser has abstained from words, there is a lot of yellow color. the drug for 10 days. Speed at work • One man (In USA) who was a construction worked took ‘street’ speed to increase his productivity/ keep awake etc. • His levels of paranoia were so high that he hallucinated that his foot was speaking to him • So he cut it off “Get him a psyche consult” • Moderately high Dopamine levels make us onguard, suspicious, and prone to misinterpret experiences in the environment. • Known as an “idea of reference” in psychiatry, we begin thinking unrelated experiences are suddenly directly related to us. People observed talking across the street are now talking about us. • As Dopamine increases, it can become so intense that we feel the radio, television, and newspaper contain secret messages directed at us from Hollywood or elsewhere. “He’s a different person” • It’s as though we are attempting to incorporate/add everything we witness into our life • In an attempt to make sense, we may become extremely religious, paranoid, or feel we are a very important person (‘Napoleon’ syndrome) • Our mind speed increases and races in an attempt to add all we see into our life. • Planes flying overhead are snapping pictures of us and motorists talking on cellular phones are calling in a report on us • Increased Dopamine also increases the perception of our senses, as though turning up the volume in all our senses – hearing, vision, taste, smell, and touch. Psychological conditions • Dopamine levels typically change very slowly. Patients who develop Paranoia and/or Schizophrenia often experience a gradual increase in Dopamine levels over several years – also experiencing an increase in the severity of symptoms over those years • A typical A-level student may develop a sense of being on-edge or unusual feelings, gradually becoming suspicious and feeling alienated, moving into auditory hallucinations, and finally developing bizarre false beliefs (delusions) of persecution or exaggerated self-importance over the next several years. • Stress can often rapidly increase Dopamine, but it still rarely happens overnight.