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PSYC370 Ch 15.pdf

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Queen's University
PSYC 370
Janet L Menard

PSYC  370   Chapter  15   Drug  Addiction  and  the  Brain’s  Reward  Circuits     Pharmacology:  scientific  study  of  drugs.     Basic  principles  of  drug  action     Psychoactive  drug:  drug  that  acts  on  the  nervous  system,  and  influence  subjective  experience   and  behaviour.     Routes  of  administration:   -­‐ Oral   -­‐ Injection   -­‐ Inhalation   -­‐ Mucous  membranes     Oral  ingestion   -­‐ Once  drugs  are  digested  partially  by  stomach  fluids   -­‐ Absorbed  into  bloodstream  via  the  small  intestine     Some  drugs  are  absorbed  through  the  stomach  wall  (e.g.,  alcohol)  and  therefore  have  quicker   effects.       -­‐ If  drugs  are  not  absorbed  in  the  GI  tract  or  they  are  broken  down  by  metabolites,  then  they   must  be  administered  by  another  route     Advantages   Disadvantages   -­‐ Safe   -­‐ Unpredictable  absorption   -­‐ Easy     Injection   -­‐ Subcutaneous  (SC)   -­‐ Intramuscular  (IM)   -­‐ Intravenous  (IV)   -­‐ Drug  moves  directly  to  the  brain     Subcutaneous  injection:  into  fatty  tissue  beneath  the  skin.   Intramuscular  injection:  into  large  muscles.     Intravenous  injection:  directly  into  veins  at  points  where  they  are  close  to  the  skin.     -­‐ Preferred  by  drug  addicts           15  :  1   PSYC  370   Advantages   Disadvantages   -­‐ Fast   -­‐ Effects  cannot  be  undone  once   -­‐ Direct   administration  has  taken  place   -­‐ Infection   -­‐ Scar  tissue   -­‐ Collapsed  veins     Inhalation:  drug  is  absorbed  into  the  bloodstream  via  capillaries     Disadvantages:     -­‐ Difficult  to  control  dose   -­‐ Lung  damage  with  chronic  use     Mucous  membrane  absorption:  drugs  can  be  administered  through  the  mucous  membranes  in   the  nose  (e.g.,  snorting),  mouth,  and  rectum.     Disadvantage:   -­‐ Damage  to  tissues  with  chronic  use     Penetration  of  the  central  nervous  system  –  drug  enters  the  bloodstream  and  is  carried  to  the  CNS.   The  blood-­‐brain  barrier  makes  it  difficult  for  many  drugs  to  enter  the  brain.     Mechanisms  of  drug  action   -­‐ Diffuse  binding   -­‐ Binding  to  particular  receptors   -­‐ Influencing  synthesis,  transport,  release,  or  deactivation  of  NTs   -­‐ Influencing  chain  of  chemical  reactions  that  occur  in  postsynaptic  neurons     Drug  metabolism:  conversion  of  psychoactive  drug  into  a  nonactive  form;  usually  works  by   eliminating  drug’s  ability  to  pass  through  cellular  membranes.   -­‐ Enzymes  excreted  by  the  liver   -­‐ Drugs  can  be  excreted  from  the  body  while  active  (in  urine,  sweat,  feces,  breath,  and  milk)                               15  :  2   PSYC  370   Drug  tolerance.     Drug  tolerance:  decreased  sensitivity  to  the  effects  of  a  drug  caused  by  exposure.  Manifestations:   -­‐ Same  quantity  of  drug  has  diminished  effects   -­‐ Same  effect  of  drug  requires  larger  quantities     Notice  that  the  dose-­‐response  curve  shifts   to  the  right  due  to  tolerance.  Note  what  this   means.  Note  what  the  graph  looks  like,   represents,  and  the  axes.     Cross-­‐tolerance:  a  drug  can  produce   tolerance  to  the  effects  of  another  drug  that   works  by  similar  mechanisms.     Sensitization:  increasing  sensitivity  to  a  drug.       3  important  points  on  the  specificity  of  drug  tolerance   -­‐ Drugs  can  produce  tolerance  to  other  drugs  that  work  by  the  same  mechanism  (cross-­‐ tolerance)   -­‐ Tolerance  can  develop  to  some  effects  but  not  others,  and  sensitivity  to  a  drug  can  increase   for  some  effects  but  not  others   -­‐ There  are  many  different  mechanisms  that  cause  drug  tolerance  –  these  vary  with  the  drug   type  (and  subsequently  how  it  acts  on  the  brain)     Look  at  that  last  point  again.  Even  though  there  is  no  unitary  mechanism  of  drug  tolerance,  the   changes  in  the  brain  that  occur  with  drug  tolerance  can  be  broken  down  into  two  categories.       Metabolic  tolerance:  structural  changes  in  the  brain  causing  tolerance  by  reducing  the  drug’s   accessibility  of  the  receptor  sites.       Functional  tolerance:  drug  tolerance  caused  by  reduced  reactivity  at  the  receptor  site  (i.e.,   diminished  signal  when  the  drug  binds).  Different  neural  changes  (mechanisms):   -­‐ Reduced  number  of  receptors   -­‐ Decreased  binding  efficiency   -­‐ Diminished  activity  upon  binding     Withdrawal  and  physical  dependence.     Withdrawal  syndrome:  individual  experiences  effects  that  are  the  opposite  of  the  normal  effects   of  the  drug.  Occurs  when  there  is  a  large  reduction  in  the  level  of  drug  in  the  body.       Physical  dependence:  an  individual  is  physically  dependent  on  a  drug  if  he  or  she  experiences   withdrawal  syndrome  in  the  absence  of  the  drug.         15  :  3   PSYC  370   Theory  of  withdrawal:       Frequent   and   large   amounts   of   a   drug   trigger   tolerance   to   a   drug.   This   results   in   neural   or   structural   changes   to   offset   the   drug   effects.   When  the  drug  is  not  in  the  body,  the  endogenous   NTs   do   not   have   the   same   signal   strength   that   they  did  before  drug  tolerance,  due  to  one  of  the   reasons  listed  under  functional  tolerance  on  the   previous  page.  This  is  said  more  eloquently  in  the   figure.                         Addiction.     Addicts:  habitual  drug  users  who  continue  to  use  a  drug  despite  its  adverse  effects  on  their  health   &  social  life,  and  despite  numerous  attempts  to  stop  using.       Cycles  of  physical  dependence,  withdrawal,  and  using  to  alleviate  withdrawal  symptoms  does  not   explain  the  processes  going  on  in  addiction.   -­‐ Relapse  after  long  recovery     Role  of  learning  in  drug  tolerance     -­‐ Contingent  drug  tolerance   -­‐ Conditioned  drug  tolerance     Contingent  drug  tolerance:  tolerance  only  develops  to  drug  effects  that  are  experienced.       Before-­‐and-­‐after  design:  two  groups  go  through  the  same  manipulation  (e.g.,  drug   administration)  and  testing,  but  some  are  dosed  before  the  task  and  some  are  dosed  after.  The  DV   occurs  when  all  subjects  are  given  a  dose  of  the  drug  and  tested  on  the  task.             15  :  4   PSYC  370   Contingent  drug  tolerance   experiment  with  rats.       1. roup  was  given  alcohol  before   a  convulsive  stimulation.   2. roup  was  given  alcohol  after   convulsive  stimulation.     Both  groups  received  the   same  dose  at  the  same   frequency  and  participated  in   the  same  tasks  (before-­‐and-­‐ after  design).         Results:  notice  the  dots  close  to  the  x-­‐axis.  These  represent  that  the  alcohol  had  an  anticonvulsant   effect  (lowered  seizure  duration)  on  the  rats.  Group  1  (lighter  line)  developed  tolerance  to  the   anticonvulsant  effects.  Group  2,  who  always  received  the  alcohol  after  the  convulsive  stimulation,   had  experienced  the  same  drug  at  the  same  dose,  and  yet  did  not  become  tolerant  to  the   anticonvulsant  property  on  test  day.     Conditioned  drug  tolerance:  expression  of  drug  effects  depends  on  the  setting  in  which  drugs   are  taken.       Conditioned  drug   tolerance  experiment  with   rats.     Both  groups  were  injected   with  alcohol  on  one  day  and   saline  the  next.  This  pattern   repeated  for  20  days.     1. roup  was  injected  with   alcohol  in  a  distinctive  test   room  and  with  saline  in  the   colony  room.     2. roup  was  injected  with   alcohol  in  the  colony  room   15  :  5   PSYC  370   and  with  saline  in  the  distinctive  test  room.   Results:  look  at  the  results  of  the  testing  in  the  previous  figure.  Rats  showed  tolerance  (i.e.,  no   change  in  body  temperature)  when  tested  in  the  same  room  where  drug  administration  took  place   and  experienced  the  regular  hypothermic  effects  when  the  drug  was  administered  in  a  different   room  than  usual.       Situational  specificity  of  drug  tolerance:  refers  to  the  fact  that  the  body  may  experience  drug   tolerance  in  a  familiar  setting  but  not  experience  tolerance  in  novel  (administration)  settings.     -­‐ Why  overdose  is  more  common  in  a  novel  context     Conditioned  stimuli  can  include  bars,  washrooms,  needles,  other  addicts  –  anything  that  predicts   use  of  the  drug.     Conditioned  compensatory  responses:  stimuli  that  predict  drug  administration  condition  the   body  to  respond  physiologically  with  effects  opposite  to  those  of  the  drug.     Exteroceptive  stimuli:  external,  public  stimuli.     Interoceptive  stimuli:  internal,  private  stimuli.   -­‐ Thinking  about  the  drug  can  cause  conditioned  compensatory  responses     Sensitization  (recall  drug  sensitivity:  increased  sensitivity  to  the  effects  of  a  drug)  can  also  be   situational.  For  instance,  sensitization  effects  occur  only  in  settings  where  the  drug  has  been   previously  administered.       Withdrawal   Compensatory  responses   -­‐ Effects  opposite  to  those  of  the  drug   -­‐ Effects  opposite  to  those  of  the  drug   -­‐ Caused  by  removal  of  drug  from  the   -­‐ Caused  by  cues  that  typically  predict   body   drug  administration     The  text  discusses  the  problem  with  Siegel’s  application  of  Pavlovian  condition  to  conditioned   compensatory  effects.  I  don’t  really  understand  what  they’re  saying,  so  pay  extra  attention  to  the   lecture  notes.     Commonly  abused  drugs     -­‐ Tobacco   -­‐ Alcohol   -­‐ Marijuana   -­‐ Cocaine   -­‐ Opiates     Nicotine  acts  on  nicotinic  cholingeric  receptors.       15  :  6   PSYC  370   Tar:  collective  name  of  the  over  4,  000  chemicals  in  tobacco.   Tolerance  in  tobacco  –  see  chart  of  effects.     Nonsmokers   Smokers   -­‐ Nausea   -­‐ Tolerance  to  effects  listed  for   -­‐ Vomiting   nonsmokers   -­‐ Coughing     -­‐ More  relaxed   -­‐ Abdominal  cramps   -­‐ More  alert   -­‐ Dizziness   -­‐ Less  hunger   -­‐ Flushing     -­‐ Diarrhea     Compulsive  craving  –  the  defining  feature  of  drug  addiction.     Percentage  of  users  who  become  addicted   -­‐ Tobacco  =  70%   -­‐ Heroin  =  30%   -­‐ Alcohol  =  10%     Only  20%  of  smoking  cessation  efforts  are  successful  for  more  than  two  years.     Smoker’s  syndrome:  symptoms  of  chest  pain,  laboured  breathing,  wheezing,  coughing,  and   vulnerability  to  respiratory  tract  infections.     Smokers  more  vulnerable  to   -­‐ Bronchitis   -­‐ Pneumonia   -­‐ Emphysema   -­‐ Cardiovascular  disease   -­‐ Cancer   - Lung   - Larynx   - Mouth   - Esophagus   - Kidneys   - Pancreas   - Bladder   - Stomach     Buerger’s  disease:  blood  vessels  in  the  legs  become  constricted;  occurs  mostly  in  male  smokers.     -­‐ Causes  gangrene     Teratogen:  substance  that  interferes  with  the  normal  development  of  the  fetus.     Alcohol  molecules  are  soluble  in  fat  and  water.  This  means  that  molecules  can  enter  all  parts  of  the   body.   15  :  7   PSYC  370     Depressant:  substance  that  suppresses  neural  firing.       Alcohol  is  a  depressant  at  moderate  and  high  levels.  At  low  levels  it  can  enhance  neural  firing.     Genetic  component  of  alcohol  addiction  –  heritable  (55%)  and  several  genes  implicated.     Alcohol  can  cause  death  by  respiratory  depression  when  blood  alcohol  level  is  at  0.5%.       Hypothermic  effect  of  alcohol  –  dilation  of  red  blood  vessels  in  the  skin  causes  more  body  heat  to   be  lost  to  the  environment.     Diuretic:  substance  that  increases  urine  production  by  the  kidneys.     Most  alcohol  tolerance  is  functional  tolerance.  Some  metabolic  tolerance  does  occur,  in  that  the   livers  of  heavy  drinkers  breakdown  alcohol  faster  than  the  livers  of  nondrinkers.       Mild  alcohol  withdrawal  manifests  as  a  hangover:  headache,  nausea,  vomiting.     3  phases  of  alcohol  withdrawal  syndrome   Phase  &  Onset   Symptoms   1. 5  –  6  hours  after  cessation  of  heavy  drinking   -­‐ Severe  tremors   -­‐ Agitation   -­‐ Headache   -­‐ Nausea   -­‐ Vomiting   -­‐ Abdominal  cramps   -­‐ Profuse  sweating   -­‐ Hallucinations     2. 15  –  30  hours  after  cessation   -­‐ Convulsions     3. One  –  two  days  after  cessation   -­‐ Delirium  tremens   -­‐ Hallucinations   -­‐ Delusions   -­‐ Agitation   -­‐ Confusion   -­‐ Hyperthermia   -­‐ Tachycardia     -­‐ Can  be  lethal   -­‐ Lasts  3  –  4  days     Alcohol  causes  direct  and  indirect  brain  damage.       15  :  8   PSYC  370     Effects  of  alcohol  on  the  brain   -­‐ Reduced  flow  of  Ca ions  into  neurons   -­‐ Interferes  with  second  messengers   -­‐ Disruption  of  GABAergic  and  glutaminergic  transmission   -­‐ Apoptosis     Physical  effects  of  alcohol   -­‐ Cirrhosis:  scarring  of  the  liver;  can  be  lethal.   -­‐ Erodes  heart  muscles   -­‐ Irritates  digestive  tract  lining   -­‐ Pancreatitis:  inflammation  of  the  pancreas.   -­‐ Gastritis:  inflammation  of  the  stomach.       -­‐ Traffic  accidents     Symptoms  of  fetal  alcohol  syndrome:   -­‐ Brain  damage   -­‐ Mental  retardation   -­‐ Poor  coordination   -­‐ Poor  muscle  tone   -­‐ Low  birth  weight   -­‐ Retarded  growth   -­‐ Physical  deformity     Treatments  for  alcoholism   -­‐ Disulfiram:  interferes  with  metabolism  of  alcohol,  which  causes  blood  accumulation  of   acetaldehyde  (unpleasant).     Studies  have  found  that  moderate  drinking  does  not  truly  lower  incidence  of  cardiovascular   disease.  The  initial  trend  was  correlational  and  did  not  consider  that  many  of  the  individuals  in  the   “abstainers”  group  had  once  drank  but  stopped  because  they  became  ill  (for  other  reasons).     Cannabis  sativa:  the  common  hemp  plant.  Its  dried  leaves  are  called  marijuana.     Cannabinoids:  class  of  chemical  found  in  the  cannabis  sativa  plant.     Marijuana  contains  over  80  psychoactive  cannabinoids,  including  THC.  Most  of  the  psychoactive   effects  of  marijuana  are  caused  by  THC.       Hashish:  made  from  the  dried  resin  of  the  cannabis  sativa  plant.     Narcotic:  legal  term  used  usually  to  classify  opioids.     High  doses  of  marijuana  impact  functioning   -­‐ Impaired  memory   15  :  9   PSYC  370   -­‐ Difficulty  carrying  out  tasks  that  involve  steps   Tolerance  develops.  Withdrawal  symptoms  are  rare.       -­‐ 10%  of  users  use  dai
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