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Dopamine

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					    Dopamine



     Structure and Function
John Hill and Natalia Toporikova
         What is Dopamine?

   Dopamine (DA) is a monoamine
    neurotransmitter that upon binding to a
    dopamine receptor (G-protein coupled)
    releases a variety of downstream signals.
  Dopamine synthesis




Precursor of dopamine is amino acid tyrosine
 Where is Dopamine formed?
 Dopamine is mainly synthesized in areas
  of the central and peripheral nervous
  systems, such as in the hypothalamus, the
  arcuate nucleus, and the caudad
          How does dopamine work?
      Dopamine is released into
       synaptic cleft.
      Dopamine binds with receptor.
      Once done, dopamine is taken
       back into the cell, so not too
       much is present in the cleft.
      The control mechanism for this
       signaling is found in the
       endorphin (pink).
      Endorphin can either enhance
       of inhibit the action of
       dopamine.

Note: this is similar to what we learned about acetylcholine release.
     What are the Functions of
           Dopamine?
Dopamine plays a significant role in the
 cardiovascular, renal, hormonal, and central
 nervous systems. It is thought to control
 processes as diverse as movement to drug
 addiction.
 Dopamine dendrites extend into various regions
 of the brain, controlling different functions
 through the stimulation of α and β adrenergic
 and dopaminergic receptors (D1 and D2)
Functions of Dopamine in the Body

     Function depends on type of receptor.
      – Involved in pleasure (cocaine blocks its
        reuptake)
      – Involved in motor control of muscles in body.
      – Assists in normal brain function (thoughts)
      – Induces emotions.
    Dopamine-related diseases
 Dopamine deficiency in the striatum or substantia
  nigra results in Parkinson’s-like symptoms. In this
  case, movement becomes slow and rigid,
  accompanied by muscle tremor.
 An excessive amount of dopamine is affiliated
  with schizophrenia, characterized by altered
  behavior, and delusions.
 A deficiency of dopamine (DA) is a leading
  candidate for the etiology of certain symptoms of
  depression.
Research involving dopamine
 May have a role in obesity
 May play a role in drug addiction
 May have a role in alcoholism
 May use dopamine derivatives to treat
  disease
Drugs can stimulate
dopamine receptors
     Some drugs are known as
      dopamine agonists.
     These drugs bind to dopamine
      receptors in place of dopamine
      and directly stimulate those
      receptors.
     They can stimulate dopamine
      receptors even in someone
      without dopamine neurons.
Drugs can fail to stimulate
   dopamine receptors
        Antagonists are drugs that bind
         but don't stimulate dopamine
         receptors.
        Antagonists can prevent or
         reverse the actions of dopamine.
        They prevent dopamine from
         attaching to receptors.
     Drugs can act directly or
indirectly on dopamine receptors

 Drugs such as cocaine and amphetamine produce
  their effects by changing the flow of
  neurotransmitters.
 These drugs are defined as indirect acting because
  they depend on the activity of neurons.
     Drugs can act directly or
indirectly on dopamine receptors

 In contrast, some drugs bypass neurotransmitters
  altogether and act directly on receptors.
 Such drugs are direct acting.
 Direct agonists stimulate dopamine receptors even
  when dopamine neurons are missing.
         Two ways to affect
          dopamine levels

 Some drugs increase dopamine by preventing
  dopamine reuptake, leaving more dopamine in
  the synapse (i.e., cocaine, methylphenidate)
 While another drug helps to release more
  dopamine (amphetamine).
How cells adapt to previous
     drug exposure
             Long-term treatment with
              dopamine antagonists
              increases the number of
              dopamine receptors.
             The receptors themselves
              become more sensitive to
              dopamine.
             This process is called
              sensitization.
How cells adapt to previous
     drug exposure
             Overstimulation decreases
               the number of receptors,
               and the remaining
               receptors become less
               sensitive to dopamine.
              This process is called
               desensitization.
      Disease and drugs can
    produce faulty sensitization

 Sensitization or desensitization normally occurs
  with drug exposure. However, addiction can
  tamper with the reuptake system.
 This disrupts the normal levels of
  neurotransmitters in the brain and can lead to
  faulty desensitization or sensitization.
Reward pathway

        Dopamine neuron
         connected with part of
         the brain that is activated
         by natural rewards and
         by artificial rewards such
         as addictive drugs.
        This part of the brain is
         called the reward
         system.
How reward pathway works
 This pathway is activated by a rewarding
  stimulus.
 The dopamine system compares the brain
  expectations of reward with what is actually
  happening at the moment.
 If the reward is higher than predicted,
  dopamine is sent to many parts of the brain,
  giving the green light to action to get more
  reward.
Cocaine addiction
         Cocaine binds to the
          uptake pumps and
          prevents them from
          removing dopamine from
          the synapse.
         More dopamine in the
          synapse, and more
          dopamine receptors are
          activated.
             Cocaine addiction
                               The increased activation of
                                dopamine receptors causes
                                increased production of
                                cAMP inside the post-
                                synaptic cell. This lead to
                                abnormal firing patterns.
                               With continued use of
A PET Scan (glucose uptake)
                                cocaine, the body relies on
                                this drug to maintain
                                rewarding feelings.
          Nicotine addiction
 Nicotinic acetylcholine receptors respond to
  nicotine as it enters the body after smoking a
  cigarette.
 That burst of activity in the neurons causes
  dopamine release that contributes to the sensation
  of pleasure.
 Over time some nicotinic receptors desensitize,
  even though nicotine is still present.
          Nicotine addiction
             mechanism.
 The first cigarette of the day gives smokers their
  first exposure to nicotine in 8-10 hours, so the
  neurons experience an extreme burst of activity.
 The dopamine system gives the signal to get more
  reward (cigarette).
 Later in the day there will be a mixture of the
  receptors being desensitized and activated, so that
  a smoker will not get the same large burst of
  activity and pleasure that the first cigarette
  provides.
Food addiction
     Obese people have about
      20% fewer receptors for
      the chemical dopamine in
      the area of the brain that
      regulates reward.
     Desensitization may
      trigger overeating in an
      effort to stimulate the
      reward pathway.
Conclusion
 Dopamine plays a major role in
  addiction.
 The activation and deactivation
  of dopamine receptors can lead
  to activation of the brain center
  responsible for pleasure.
 Dopamine is a key element in
  the reward system - the
  expectation of reward can
  change behavior.

				
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posted:8/15/2011
language:English
pages:25