Drug Addiction

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Drug Addiction

• OPIATES

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Introduction

• Brief history
• Neurotransmitters Affected
• Brain Regions Affected
• Tolerance, Withdrawal, Behavior

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Brief History

• Opiates are drugs derived from the poppy plant
• Have been used for centuries to relieve pain
• Includes opium, heroin, morphine, and codeine
• Opiates such as morphine and codeine used for
  medicinal purposes, however can be abused just
  like opium and heroin.

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History Continued

• Opiates also inhibit brain centers controlling
  coughing, breathing, and intestinal motility.
  Both morphine and codeine are used as pain
  killers, and codeine is also used in cough
  medicine.
• Opiates depress nerve transmission in sensory
  pathways of the spinal cord and brain that signal
  pain. This explains why opiates are such
  effective pain killers.

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Neurotransmitters

• Various Receptors and NTSs
• GABA
• Endorphins
• Dopamine
• Opiate Receptors

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Neurotransmitters

• Opiates bind to so-called mu (µ) receptors
• These G-protein-coupled receptors are located on
  the subsynaptic membrane of neurons involved in
  the transmission of pain signals.

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Neurotransmitters

• GABA
• Affects dopaminergic cells
• Opiates and opioid NTSs activate the presynaptic
  opioid receptors on GABA neurons
• This inhibits the release of GABA in the VTA
• Inhibiting GBA allows the dopaminergic neurons to
  fire faster

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Neurotransmitters

• Endorphins
• Called natural opiates
• Involved in glucose regulation
• Endorphins and Enkephalins are natural neural
  peptides that bind to opiate receptors to produce
  euphoric effects
• Released by brain when exposed to opiates

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Neurotransmitters

• Dopamine
• Dopaminergic cells- dopamine is manufactured,
  transported down the length of the neuron, and
  packaged for release in the synapse
• Key involvement in opioid reward
• Ventral Tegmental Area known area for DA activity
• Opioids in VTA have a rewarding affect
• Effects of opioids are contingent on dopamine
  activation

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NeurotransmittersAnimal Studies

• Dopamine
• (Agmo et al. 1990)
• Opioids have an evolutionary purpose
• Male rats used and partnered with copulatory
  females
• Rays administered nalexone, a synthetic opioid
• It is suggested that release of endogenous
  opioids renders ejaculation rewarding
• Dopamine thus seems to be of slight importance
  for that effect of copulation

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Neurotransmitters

• Dopamine
• opiates applied to the VTA increases dopamine
  activity.
• dopamine affects the rewarding properties of
  opioids in the VTA
• morphine enhances the firing frequency of
  mesolimbic DA neurons projecting from the VTA ,
  which provides evidence that opioids have an
  excitatory affect on dopamine.
• Dopamine antagonists, molecules that bind to the
  receptor and prevent it from being activated,
  block the effect of opioids by halting
  morphine-induced activities

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Neurotransmitters

• Opiate Receptors
• Presynaptically inhibit transmission of excitory
  pathways
• Pathways include acetylcholine, the
  catecholamines, serotonin, and substance P
• Substance P is a neuropeptide active in neurons
  which mediate our sense of pain

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Neurotransmitters

• Opiate Receptors
• Proteins found in the brain, where naturally
  occurring opioids bind to (i.e..endorphins)
• Opioids mimic these naturally occurring
  opioid-like molecules that are made and used in
  the brain
• Four types of opiate receptors mu, delta,
  epsilon, kappa
• Naltrexone, an opioid blocker that is being used
  for addiction

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Brain RegionsLocalization of Opiate Binding
sites

• The VTA includes
• accumbens
• caudate nucleus
• thalamus

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Brain RegionsOpiates binding to opiate
receptors in the NAC Increase dopamine release

• 3 neurons in opiate action
• Dopamine terminal
• Postsynaptic cell
• Other terminal(GABA)

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The Neural Circuit

• The Reward Pathway
• Major structures
• the ventral tegmental area
• the nucleus accumbens
• prefrontal cortex
• Other areas include
• arcuate nucleus
• Amygdala
• locus coeruleus
• periaqueductal gray area

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Tolerance

• Tolerance can be defined as the decreased potency
  of a drug, such that progressively larger doses
  must be used to achieve the same effect
• Dependence, which is closely associated with
  tolerance, involves a continued need for opioid
  administration in order to prevent withdrawal
  symptoms
• symptoms include nausea, gastrointestinal
  disturbances, chills, and a general flu-like
  state in humans
• Lesion studies indicate that no single brain
  structure is responsible for the withdrawal
  symptoms

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Withdrawal

• (Caille et al. 2003)
• Opiate withdrawal has been correlated with
  decreased extra-cellular dopamine levels in the
  nucleus accumbens (NAC) of morphine-dependent
  rats. The authors tested the hypothesis that DA
  transmission plays a critical role in the
  induction of motivational and somatic withdrawal
  symptoms.

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Behavior

• Opiates and other neurotransmitters affect
  behavior and feelings by opening and closing ion
  channels that control the firing of nerves
• The drug produces relaxation, relief of pain and
  anxiety, decreased alertness, impaired
  coordination and serious problems with
  constipation.
• Continued use may result in weight loss, mental
  deterioration and death.
• Withdrawal sickness will occur if the drug is
  discontinued. Overdose can result in stupor, coma
  and death.

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StudiesFuture Implications

• (Segall et al. 1989) found that when naloxone was
  administered, eating palatable foods was
  effectively decreased.
• Shows possible reward systems for anorexia that
  reaffirm the behavior
• important implications for the use of opioid
  antagonists in weight-loss programs

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Conclusion

• One of the most detrimental side effects of opium
  is addiction
• Opium addiction occurs very rapidly, sometimes
  within weeks
• Continued use of the drug occurs not only for the
  purpose of intoxication, but too avoid the
  painful side effects associated with withdrawal
  that naturally come with opiate addiction
• Thus, more studies should be done on synthetic
  opiates (I.e. naloxone) in order to aid in
  overcoming addiction

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Interesting Fact

• Unlike the information portrayed in the popular
  sitcom Seinfeld
• You would have to ingest 10 lbs. of poppy seeds
  in order to feel any opiate like effects, or even
  test positive for drugs such as heroin