Title: When Good Brains Go Bad Behavior and Disease: Depression and Addiction
1When Good Brains Go BadBehavior and Disease
Depression and Addiction
- SHP Neurobiology of Development and Disease
The Scream by Edvard Munch
2Brain vs Mind
Mind Blowing by Nicolas Cann
- To what extent does your brain determine who you
are? - Your personality.
- Your individuality.
- Your desires.
3- brain n.
- The portion of the vertebrate central nervous
system that is enclosed within the cranium,
continuous with the spinal cord, and composed of
gray matter and white matter. It is the primary
center for the regulation and control of bodily
activities, receiving and interpreting sensory
impulses, and transmitting information to the
muscles and body organs. It is also the seat of
consciousness, thought, memory, and emotion. - A functionally similar portion of the
invertebrate nervous system. - Intellectual ability mind a dull brain a quick
brain. - Intellectual power intelligence. Often used in
the plural has brains and good looks. See
Synonyms at mind. - A highly intelligent person.
- The primary director or planner, as of an
organization or movement. Often used in the
plural. - The control center, as of a ship, aircraft, or
spacecraft.
From www.dictionary.com
4- mind n.
- The human consciousness that originates in the
brain and is manifested especially in thought,
perception, emotion, will, memory, and
imagination. - The collective conscious and unconscious
processes in a sentient organism that direct and
influence mental and physical behavior. - The principle of intelligence the spirit of
consciousness regarded as an aspect of reality. - The faculty of thinking, reasoning, and applying
knowledge Follow your mind, not your heart. - A person of great mental ability the great minds
of the century. - Individual consciousness, memory, or
recollection I'll bear the problem in mind. - A person or group that embodies certain mental
qualities the medical mind the public mind. - The thought processes characteristic of a person
or group psychological makeup the criminal
mind. - Opinion or sentiment He changed his mind when he
heard all the facts. - Desire or inclination She had a mind to spend
her vacation in the desert. - Focus of thought attention I can't keep my mind
on work. - A healthy mental state sanity losing one's
mind.
From www.dictionary.com
5Phineas Gage
- On Sept 13, 1848 Gage was working in railroad
track construction outside Cavendish, VT when a
tamping iron, driven by detonation of a blasting
charge, passed through his anterior frontal
cortex. - He regained consciousness within minutes, could
speak and was stable. - Later, he was reported to suffer from broad
personality changes - Gage was fitful, irreverent, indulging at times
in the grossest profanity (which was not
previously his custom), manifesting but little
deference for his fellows, impatient of restraint
or advice when it conflicts with his desires, at
times pertinaciously obstinate, yet capricious
and vacillating, devising many plans of future
operations, which are no sooner arranged than
they are abandoned in turn for others appearing
more feasible. A child in his intellectual
capacity and manifestations, he has the animal
passions of a strong man. Previous to his injury,
although untrained in the schools, he possessed a
well-balanced mind, and was looked upon by those
who knew him as a shrewd, smart businessman, very
energetic and persistent in executing all his
plans of operation. In this regard his mind was
radically changed, so decidedly that his friends
and acquaintances said he was 'no longer Gage'. - Dr. J.M. Harlow (Gages Physician)
6We will address the development/adaptation and
pathogenesis of two behaviors
7Anxiety
- Behavioral response that allows individuals to
become aware to dangers in their environment. - Often genetically linked. An immediate relative
can predispose an individual to an anxiety
condition. - 25 of all adults will, at one point in their
lives, experience an anxiety condition - Economic cost of disorder is an estimated 40
million a year
86 Types of Anxiety Disorders
- Panic disorder unpredictable, intense anxiety
attacks - Generalized anxiety disorder excessive worry in
multiple areas - Social anxiety disorder fear and avoidance of
social situations - Specific phobia intense fear with a specific
trigger (spiders, dark water etc) - Posttraumatic stress disorder intrusive,
anxiety-provoked memories of trauma - Obsessive-compulsive disorder anxious obsessions
and anxiety-reducing compulsive behaviors
Gordon and Hen, 2004
9(No Transcript)
10Serotonergic Circuit
- Majority of neurons releasing serotonin are
present in the Raphe nuclei of the hindbrain - Primary site of innervation is the limbic system
(hippocampus, amygdala, entorhinal cortex,
hypothalamus)
11Noradrenergic Brain Circuit
- Norepinephrine producing neurons lie in the locus
coeruleus - These neurons project to the nucleus accumbens
and the hypothalamus, where they mediate anxiety
and arousal, respectively.
12Basal Anxiety is Determined During a Critical
Period in Development
Rescue of serotonin receptor in early development
rescues anxiety phenotype in knockout animals
13Three Classes of Drugs are Used to Treat
Anxiety/Depression
14Anxiolytic Mechanisms
15Mechanism of GABA Agonists
- Barbiturates, benzodiazepines and GABA have
individual binding sites on the GABA channel. - Binding of more than one ligand at a time can
potentiate opening of the channel ? increased
conductance
16Using Mice as a Behavioral Model of Anxiety
- Mice avoid open, well-lighted areas and novel
environments (where they may be more vulnerable
to predators) - Starved mice are placed in an open area with food
in the center - Measure the latency until mouse eats the food
pellet. - This can be taken as a measurement of the anxiety
of the mouse. Anxiolytic drugs (like
benzodiazepines) decrease the latency.
Santarelli et al, 2003
17Antidepressant Drugs Increase Neurogenesis
- Rats are injected with bromo-deoxyuridine (BrdU)
after treatment with an antidepressant drug. - BrdU is taken up into proliferating cells and you
can detect these cells by immunohistochemistry - These cells can be quantified for a value of
proliferation in a tissue under a given
condition/treatment.
Marburg et al, 2000
18Control Checklist
- BrdU is incorporated into proliferating cells in
the hippocampus and these develop into neurons
(NeuN positive cells) and glia (GFAP positive
cells) - Administration of fluoxetine (F), imipramine (I),
desipramine (D), or DPAT (5-HT) agonist are
administered - Neurogenesis increases with treatment with all
drugs acutely - Treatment with all drugs decreases latency to
novelty suppressed feeding
Santarelli et al, 2003
19X-ray Ablation of Neurogenesis in the Dentate
Gyrus
Santarelli et al, 2003
20Addiction
21Addiction morbidity
- 2 billion alcohol users, 1.3 billion tobacco
users, 185 million users of illicit drugs (WHO
reports) - In 2001, these catagories contributed to 12.4 of
deaths worldwide
22Vocabulary
- Addiction increase in drug-seeking behavior
- Reinforcement drug enhancing a desire to repeat
the use of the substance in the future - Dependence need for continued use of the drug to
avoid withdrawal symptoms - Withdrawal physical or motivational disturbances
when consumption of the drug is ceased - Tolerance/sensitization specific effects of the
drug diminish under that same dosage regiment
234 Criteria for Abuse
7 Criteria for Dependence
- The need for markedly increased amount of the
substance to achieve intoxication or desired
effect, or diminished effect with continued use
of the same amount (tolerance) - Withdrawal syndrome or use of the substance to
relieve or avoid withdrawal symptoms - One or more unsuccessful attempts to cut down or
control use - Use in larger amount over a longer period than
intended - Important social, occupational or recreational
activities are given up or reduced because of
substance use - A larger amount of time is spent in activities
that are necessary to obtain, to use or to
recover from the effects of the substance - Continued use despite knowledge of having
persistent or recurrent physical or psychological
problems that are caused or exacerbated by the
substance
- Recurrent use resulting in a failure to fulfill
the main obligations at work, school or home - Recurrent substance-related legal problems
- Recurrent use in physically hazardous situations
- Continued use despite persistent or recurrent
social or interpersonal problems that are caused
or exacerbated by the substance
24The Circuits of Motivation
- Circuits for motivation and reward are ancient
and beneficial for the survival of the organism
as it makes them seek out things they need (food,
water, sexual opportunities) and provides a
reinforcement when it has been attained. - Motor motivation has long been known to be
centrally driven by dopaminergic centers
(Parkinsons Disease). - Damage to specific dopaminergic fibers was shown
to generate feeding and drinking deficits. - Administration of neuroleptics (inhibitors of
dopamine signaling) diminish the animals desire
to seek out food and water.
25Identification of the Reward Circuit
- Olds and Milner in 1954 identify sites in the
brain (lateral hypothalamic and septal sites)
which confer pleasure and reward - When electrodes are placed in these regions, rats
will self-stimulate by pressing a lever. - Rats pressed the constantly (10,000 per hour)
and, given a choice between food/water and the
stimulation, will allow themselves to starve to
death. - This self-stimulation is blocked by
administration of the dopaminergic inhibitor,
pimozide.
Wise et al, 2004
26Reward Circuit
By repeating the intracranial self-stimulation
experiments in different brain areas (but with
drugs instead of current), the target of a number
of drugs of abuse have been identified
27Stimulation of Reward Pathway Overcomes Aversive
Tendencies
- By stimulating the reward pathway, investigators
were able to make a remote-controlled rat. - Electrodes are placed into whisker
representations on each side of the brain and
into the nucleus accumbens - If stimulation of a whisker representation is
followed by a stimulation of the nucleus
accumbens, the rats learn to follow these
directions. - Rats can be controlled in to the open field and
elevated novel areas without latency