Biological Basis of Behavior:

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Biological Basis of Behavior

• Psychopharmacology Presentation

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The Relationship between the Brain, Mental
Illness Pharmacology
Nancy McQuade Kelly Veneziano
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Transmission of Messages in the Brain via
Neurotransmitters

• Mechanisms
• Neurons nerve cells which synthesize chemicals
  that serve as neurotransmitters.
• Axon thin fiber that serves as
  information-sender of the neuron, conveying an
  impulse toward either other neurons or a gland or
  muscle.
• Dendrites branching fibers off of the soma or
  cell body that are lined with synaptic receptors
  where the dendrite receives information from
  other neurons.
• Presynaptic Terminal swelled tip of the axon at
  which point the axon releases chemicals.
• Postsynaptic Terminal

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Neurotransmitters

• Types
• Dopamine mostly an inhibitory transmitter,
  therefore drugs that increase the activity at
  dopamine synapses decrease the activity in much
  of the brain.
• Serotonin - interacts with norepinephrine to
  cause depression.
• Norepinephrine - believed to be a causative
  factor for depression.
• GABA inhibits anxiety
• Acetylcholine
• Histamine

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Pharmacologic Agents

• Mechanisms Drugs influence synaptic activity in
  many ways. Drugs can increase or decrease the
  synthesis of the neurotransmitter, cause it to
  leak from its vesicles, increase its release,
  decrease its reuptake, block its breakdown into
  active chemicals, or directly stimulate or block
  the postsynaptic receptors.
• Action Types
• Agonist (Excitatory) mimics and increases the
  effects of the neurotransmitter.
• Antagonist (Inhibitory) blocks the effects of
  the neurotransmitter.
• Mixed Agonist-Antagonist (Excitatory/ Inhibitory)
  acts as an agonist for some behavioral effects
  of the neurotransmitter and an antagonist for
  others or it can be an agonist at some doses and
  an antagonist at other doses.

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Classes of Psychotropic Medication

• Psycho-Stimulant Agents
• (Cylert, Dexedrine, Ritalin, Adderall)
• Anti-Depressant Agents
• (Paxil, Prosac, Elavil, Sinequan, Tofranil,
  Anafranil, Nardil,
• Parnate, Marplan)
• Anti-Psychotic Agents
• (Risperdal, Haldol, Stelazine, Thorazine,
  Mellaril)
• Anti-Manic Agents
• (Lithium, Tegretol, Depakote, Carbamazepine)
• Anti-Anxiety Agents
• (Ativan, BuSpar, Klonopin, Valium, Xanax)

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Psycho-Stimulant Agents

• Mechanism of Action (Agonist) - Stimulants
  directly increase activity at the dopamine
  receptors (especially D2, D3 and D4 receptor
  types).
• Amphetamine (in Adderall) - (Agonist)
  stimulates dopamine synapses by increasing the
  release of dopamine from the presynaptic
  terminal. The presynaptic terminal ordinarily
  reabsorbs released dopamine through a protein
  called dopamine transporter. Amphetamine
  reverses the transporter, causing the cell to
  excrete dopamine instead of reabsorb it.
  Amphetamine also blocks certain synapses that
  inhibit dopamine release so it works in two ways.
  The behavioral effects of Amphetamine and Cocaine
  are similar because they both increase dopamine
  activity. Both have intense, short acting effects
  which lead to crashes within a few hours and
  causes addiction.
• Methylphenidate (Ritalin) (Agonist) blocks the
  reuptake of dopamine (similar to Cocaine but
  different in its gradual increase in
  concentration in the brain in its pill form).
  Methylphenidate also increases serotonin release,
  which may have some calming effects on some
  hyperactive people/
• Effects Stimulants produce excitement,
  alertness, elevated mood, and sometimes increased
  motor activity.
• Uses and Target Disorders (ADD/ADHD) ADD/ADHD
  is a disorder marked by impulsiveness and poor
  control of attention (and in some cases
  hyperactivity).

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ADD/ADHD

• ADHD is a biologically explainable disorder.
• Children with ADHD dont produce enough dopamine.
• The amount of dopamine present in the synaptic
  cleft will determine how much the postsynaptic
  neuron is activated.
• The amount of activity in a given brain is
  determined by the amount of dopamine present in
  the synaptic clefts.
• Neurostimulants increase the activity at the
  dopamine receptors thereby allowing the synthesis
  of dopamine.
• Locus of Brain Involvement
• Frontal cortex (executive functioning),
• Prefrontal cortex prefrontal cingulate
  (attention shift SCATTERED),
• Midline thalamus upper brainstem (sustained
  attention DISTRACTIBLE),
• Amygdala hippocampus (encoding INATTENTIVE),
• Inferior parietal, superior temporal, basil
  ganglia (focus/execute DISORGANIZED)

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ADD/ADHD
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Anti-Depressant Agents

• Types and Mechanisms of Action
• Serotonin Re-Uptake Inhibitors (SSRIs Paxil,
  Prosac)- (Agonist) blocks the reuptake of
  serotonin by the presynaptic terminal, as a
  result neurotransmitters remain longer in the
  synaptic cleft and continue stimulating the
  postsynaptic cell. SSRIs produce only mild side
  effects.
• Mild nausea or headache
• Nervousness - therefore it is not recommended for
  patients with comorbidity of depression and
  anxiety.
• Tricyclic Metracyclics (Elavil, Sinequan,
  Tofranil, Anafranil) (Agonist) operate by
  preventing the presynaptic neuron from
  reabsorbing serotonin or catecholamines after
  releasing them, as a result neurotransmitters
  remain longer in the synaptic cleft and continue
  stimulating the postsynaptic cell. Tricyclics
  also block histamine receptors, acetylcholine
  receptors and certain sodium channels which lead
  to side effects.
• Histamine block produces drowsiness
• Acetylcholine block causes dry mouth and
  difficulty urinating.

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Anti-Depressant Agents

• Monoamine Oxidase Inhibitors (MAOIs Nardil,
  Parnate, Marplan) - (Agonist) block the enzyme
  monoamine oxidase thereby making more transmitter
  available for release at the presynaptic
  terminal. Used for patients who dont respond to
  the Tricyclics. People taking these must avoid
  food containing tyramine, including cheese,
  raisins, pickles, licorice, etc. Tyramine
  combines effects with MAOIs thereby increasing
  blood pressure which can be fatal.
• Atypical Anti-Depressants (Wellbutrin, Velafaxin)
  - a miscellaneous group of drugs with
  antidepressant effects but only mild side
  effects. These drugs are often effective for
  patients who failed to respond to other drugs
  (Kalat, 2004, p. 467)
• Wellbutrin (Agonist) inhibits the reuptake of
  dopamine and to some extent norepinephrine but
  not serotonin.
• Velafaxin (Agonist) inhibits the reuptake of
  serotonin but also somewhat that of
  norepinephrine and slightly that of dopamine.
• Uses and Target Disorders Major Depressive
  Disorder, Dysthymic
• 
  Disorder

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Depression

• Depression is associated with a chemical
  imbalance in the brain.
• Serotonin
• Norepinephrine
• Dopamine
• Locus of Brain Involvement Research shows
  neuron shrinkage in certain areas of the
  hippocampus and cerebral cortex when people
  become depressed. As antidepressant drugs
  increase dopamine release they also increase the
  neurotrophin release and thereby increase cell
  size in the brain areas that have shown
  decreases.

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Anti-Psychotic Agents

• Mechanism of Action
• Phenothiazines (Thorazine) (Antagonist) block
• postsynaptic dopamine receptors.
• Butyrophenomes (Haldol) - (Antagonist) block
• postsynaptic dopamine receptors.
• Atypicals
• Effects Some research suggests that people with
  
• Schizophrenia have excessive activity at
  certain dopamine
• synapses and therefore have excessive
  dopamine release.
• Antipsychotic agents are thought to be
  effective because they
• Block dopamine receptors. However, about
  one quarter of
• patients do not respond to these drugs.
• Uses and Target Disorders Schizophrenia -
  Frequently
• relieves the positive symptoms (delusions,
  hallucinations) of
• Schizophrenia. Thorazine and other
  anti-psychotic agents halt
• the progression of the disease in many
  cases if treatment
• begins early.

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Schizophrenia

• Locus of Brain Involvement The prefrontal cortex
  is the area of the brain that shows the most
  consistent signs of damage in
• Schizophrenia. Other involved areas of
  compromise include
• Significant loss of gray matter
• Enlarged ventricles
• Neurological abnormalities
• Impaired
• Colored areas are those where maximum shrinkage
  of the brain occurs during the onset of
  Schizophrenia (Daqiang Sun)

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Anti-Manic Agents

• Mechanism of Action Lithium, Valporic Acid
  (Depakote), and Carbamazepine each have a variety
  of effects on the brain. Researchers are not sure
  how Lithium and other drugs alleviate Bipolar
  Disorder.
• Valporic Acid and Carbamazepine (Mixed
  Agonist/Antagonists) - increase the activity at
  GABA synapses and block the synthesis of the
  brain chemical inositol. Valporic Acid also
  blocks the synthesis of the brain chemical
  arachidonic acid, which is generally produced
  during brain inflammation.
• Lithium (Antagonist) blocks the synthesis of the
  brain chemical inositol, which contributes to
  membrane formation, helps transport and break
  down fats, and is a precursor to a second
  messenger in neurons. Lithium also blocks the
  synthesis of the brain chemical arachidonic acid,
  which is generally produced during brain
  inflammation.
• Effects Stabilizes the mood of bipolar patients,
  preventing a relapse into either mania or
  depression. The use of mood stabilizers, like
  Lithium, must be regulated carefully a low dose
  is effective and a high dose is toxic.
• Uses and Target Disorders Bipolar Disorder, Type
  I II
• Valporic Acid and Carbamazepine are often
  recommended for patients with Bipolar II
  Disorder, characterized by depression and mild
  manic phases.
• Lithium appears to be more effective for people
  with Bipolar I Disorder, with depression and
  stronger manic phases.

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Bipolar Disorder

• Locus of Brain Involvement The main areas
  involved in Bipolar Disorder are
• Frontal and temporal lobe of the forebrain
• Prefrontal cortex
• Basil ganglia
• Limbic system
• The hippocampus has also been linked to Bipolar
  Disorder.
• Researchers have also found the cerebral cortex
  to possibly be involved in Bipolar Disorder. The
  cerebral cortex is involved in thought processes.
  It is possible that abnormalities in this part of
  the forebrain are responsible for the negative
  thoughts that are associated with depressive
  episodes of Bipolar Disorder.
• Bipolar Disorder involves dysregulation of the
  stress response system (HPA axis) causing
  extremely low tolerance for stress.

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Anti-Anxiety Agents

• Mechanism of Action Benzodiazepines (Agonist)
  Facilitate the effects of GABA, which inhibits
  anxiety.
• Effects Drugs that are intended to control
  anxiety alter activity at amygdala synapses. One
  of the amygdalas main excitatory
  neurotransmitters is cholecystokinin (CCK) which
  increases anxiety, and the main inhibitory
  transmitter is GABA, which inhibits anxiety.
  These drugs go to all parts of the brain. When
  they reach the thalamus and cerebral cortex, they
  induce sleepiness, block epileptic convulsions,
  and impair memory. These are commonly experienced
  side effects.
• Uses and Target Disorders Generalized Anxiety
  Disorder

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Anxiety Disorder

• Locus of Brain Involvement Studies show that
  people with excessive fears have a hyperactive
  amygdala. Benzodiazepines exert their
  anti-anxiety effects in the amygdala and the
  hypothalamus.
• Scientists theorize that anxiety symptoms result
  because the
• brain produces too much of the
  neurotransmitters serotonin and norepinephrine.
• Too much serotonin is associated with tension,
  while if there are high levels of norepinephrine
  in the system, a person experiences other
  physical symptoms that are associated with
  anxiety, like heart palpitations.

GABAs in the 'Hood
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Complex Disorders

• E.g. - Autism Spectrum Disorder
• Prevalence
• The CDC has recently reported that 1 in 166
  children will be diagnosed with some form of ASD.
• In PA alone by the year 2010 there will be an
  estimated 27,504 children ages 3 to 21 affected
  by autism.
• Locus of Brain Involvement
• Frontal lobes
• Hippocampus
• Temporal Lobe
• Amygdala
• Cerebellum
• Complexities of Treatment
• Cognitive-Behavioral
• Social-Emotional
• Pharmacological

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Areas of the brain identified in relation to
Mental Illness and Psychopharmacological
Intervention