Wednesday, Mar 1

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Wednesday, Mar 1
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• F. Acetylcholine
• inhibitory action at receptors in the
  parasympathetic nervous system(slows heart)
• excitatory at receptors in sympathetic nervous
  system (speeds heart)

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• excitatory at receptors in the neuromuscular
  junction - stimulates muscles
• in brain, both inhibitory and excitatory actions
• large amounts in basal ganglia,
  hippocampus/limbic system, frontal cortex

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• Relevant diseases
• Alzheimers Disease - impaired memory
  functioning, confusion
• certain muscular disorders
• Relevant drugs
• nicotine (cigarettes) - mimics Acetylcholine at
  nicotinic receptor sites
• curare - blocks nicotinic receptors and prevents
  action of acetylcholine drug for muscle
  relaxation
• Used on tip of arrow to deaden the prey - causes
  muscle paralysis. Too much - causes death.

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• G. Serotonin
• in most areas, inhibitory one path is
  excitatory
• located in Reticular Activating System of
  brainstem - important in sleep (high levels
  induce sleep)
• also located in thalamic, limbic, and cortical
  areas

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• Serotonin plays an important role in
• sleep/wakefulness cycle
• mood and emotion
• perception
• body temperature regulation
• hunger

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• Serotonin
• Relevant illnesses
• Sleep disorders
• Depression - not enough serotonin in the cortical
  excitatory circuit
• Relevant drugs
• Newer Antidepressants
• hallucinogens
• euphorics (induce sense of well-being)

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• Serotonergic Antidepressants
• Selective serotonin reuptake inhibitors (SSRIs)
• Prozac Zoloft Celexa
• Effexor Luvox Paxil Anafranil
• ( also used for Obsessive Compulsive Disorder
  and Panic Disorder)
• Other SE actions that enhance serotonin
• Serzone Remeron
• hallucinogens - LSD psilocybin mushroom
• euphorics - Ecstasy/MDMA

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• H. Opiate Peptides - endorphins enkephalins
• the brains natural painkillers (endogenous
  morphine endorphin)
• located in brainstem, midbrain and limbic areas
• involved in pain and pleasure
• released during physical stress
• Runners High

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Endorphins Relevant diseases ???? substance
abuse disorders Appear to play some role in
healing process (across diseases) Relevant drugs
opium morphine codeine heroin Oxycontin
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Consequences of Drug Exposures that Occur
Prenatally How are brain development and
behavior effected? Teratology - study of abnormal
development Teratogen - an agent that causes
abnormal development Neurobehavioral
Teratology the study of abnormal brain and
behavioral development due to prenatal exposure
to toxic agents
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• Endpoints of Abnormal Development
• Death
• Malformation
• Growth Retardation
• Functional Deficit

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Environment influences development at every
stage 1. Preimplantation - death 2. Embryonic
period - malformation, effects on growth,
functional problems 3. Fetal period - growth,
functional problems, altered differentiation,
synaptogenesis, myelination, apoptosis
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• Types of environmental influences upon
  development
• maternal health
• maternal nutrition
• infections
• drug use
• environmental chemicals
• physical restrictions or damage

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Teratogens of the CNS Radiation Antimitotic
agents (cancer treatments) Certain
illnesses Abnormal amounts of certain vitamins or
minerals Prescription drugs - Accutane (treatment
of acne) Anticonvulsants Environmental chemicals
- lead, mercury, PCBs Drugs of abuse -
alcohol Hormonal disruptors Pesticides
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• Variables Governing Susceptibility
• Gestational Age at Exposure
• Genotype
• Characteristics of Agent
• Mechanism of Action
• Amount
• Route

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• Potential Neurobehavioral Teratogens
• Psychoactive Agents known to act on the adult
  CNS - drugs, hormones
• Compounds that are harmful to the adult brain
  and behavior - Neurotoxicants

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• Known Human Neurobehavioral Teratogens
• Rubella
• Cytomegalovirus
• X-Irradiation
• Retinoic Acids
• Anticonvulsant Drugs (Phenytoin Valproic Acid
  Phenobarbital Carbamazepine)
• Drugs of Abuse (Alcohol Heroin Methadone
  Methamphetamine Cocaine)
• Methylmercury
• Lead
• PCBs

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• Causes of Behavioral Dysfunction
• Reduced Number of Neurons
• Migration Defects
• Abnormalities of Cytoarchitecture synaptic
  connections
• Neurochemical Disturbances

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• Certain principles
• Some things are evident at birth some are not.
• Generally, neurobehavioral teratogens impair the
  function of more children than the number
  affected with malformations our techniques are
  not yet good enough to detect structural brain
  abnormalities at birth.
• Some agents do not cause detectable structural
  malformations (imaging), but do compromise
  behavior.
• Agents that are harmful during pregnancy may also
  be harmful during childhood brain development.

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• Accutane pill used to treat cystic acne
• a synthetic Vitamin A (a retinoic acid)
• isotretinoin

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• Embryonic Exposure to Accutane (Isotretinoin)
• Spontaneous Abortion (40)
• Major Malformations (35)
• Prematurity 16

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• Accutane interferes with the development of
• Central Nervous System
• Craniofacial structures
• The Heart
• The Thymus and Parathyroid Glands
• Other organ systems

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Figure 1. Mental ability of children exposed to
isotretinoin during embryonic development.
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• Is vulnerability to the CNS effects of retinoic
  acid seen in adolescence?
• controversial human data suggest that some
  individuals of unspecified ages may experience
  depression, suicidality, or psychosis following
  Accutane treatment (Wysowski, Pitts, and Beitz,
  2001 Bremner, 2003)
• long term effects are unknown
• 2 studies in adolescent mice show that 21 days
  of treatment with 1 mg/kg/day 13 cis RA reduces
  hippocampal cell survival (Sakai et al, 2004) and
  reduces spatial learning (Crandall et al, 2004)
• reduced hippocampal neurogenesis has been shown
  in depression (increased during antidepressant
  treatment)