Psychopharmacology: Neurotransmitters, Drugs and Behavior

1
Psychopharmacology Neurotransmitters, Drugs and
Behavior
2
A quick review of synaptic action

• receptor types (ionotropic and metabotropic)
• receptor subtypes

3
Being a neurotransmitter What does it take?

• Exists presynaptically
• Synthesis enzymes exist presynaptically
• Released in response to action potential
• Postsynaptic membrane has receptors
• Application at synapse produces response
• Blockade of release stops synaptic function

4
The classical neurotransmitters

• Amines
• Monoamines
• catecholamines (dopamine, noradrenaline)
• indoleamines (serotonin, melatonin)
• Quaternary amines
• acetylcholine
• amino acids (glutamate, GABA)

5
Catecholamine synthesis
-this is not for torture -understanding synthesis
can be important for understanding drug action
6
Catecholamines
Dopamine
Subtantia nigra and Parkinsons disease
Mesocorticolimbic system and schizophrenia
Receptor specificity
7
Catecholamines
Noradrenergic pathways in the brain -locus
coeruleus
8
Serotonin synthesis
9
Serotonin
Serotonergic pathways in the brain -raphe, 15
subtypes, Prozac and depression
10
Acetylcholine synthesis
11
Acetylcholine
Cholinergic pathways in the brain -basal
forebrain, neuromuscular junction
12
Amino acids The workhorses of the
neurotransmitter family
Glutamate - the primary excitatory
neurotransmitter in brains GABA
(Gamma-amino-butyric-acid) - the primary
inhibitory neurotransmitter
13
The fabulous glutamate receptor
Activation of NMDA receptor can cause changes in
the numbers of AMPA receptors a mechanism for
learning?
14
The fabulous GABA receptor
Multiple binding sites
15
Peptides

• Produced in minute quantities
• often substances that are also found in areas of
  body other than brain (vasoactive intestinal
  polypeptide)
• tremendously potent and long-acting
  (neuromodulatory)
• opiates

16
The opiate story

• Opiates have been used for centuries to relieve
  pain
• Pert and Snyder found that opiates bind to
  receptors in several areas
• not until 1975 did we know of endogenous opioids
• several varieties of receptors

17
What is a drug?

• A very vague term
• all ingested substances alter bodily function
• drug is reserved for things that have
  pronounced effects when ingested in small
  quantities

18
Basic classification of drug actions

• Agonists stimulate or activate
• antagonists prevent

19
Ways that drugs can agonize

• Stimulate release
• receptor binding
• inhibition of reuptake
• inhibition of deactivation
• promote synthesis

20
Ways that drugs can antagonize

• Block release
• receptor blocker
• prevent synthesis

21
Schizophrenia
Affects about 1/100 people Begins in 20s Often
triggered by stress, illness, etc. but theres
also a genetic predisposition
22
Symptoms of schizophrenia
Positive symptoms -hallucinations, delusions,
paranoia Negative symptoms -lack of emotion,
energy, directedness
23
The dopamine theory of schizophrenia
24
Competitive binding
25
Clinical effectiveness of antipsychotics vs their
effectiveness in binding to dopamine receptors
26
Dopamine receptors in normals and schizophrenics
27
Beyond dopamine
New generation antipsychotics affect serotonin as
well Glutamate antagonists can help with
negative symptoms Schizophrenia likely affects a
host of systems perhaps by disturbing a
fundamental balance among neurotransmitters
28
Alzheimers Disease
First described by Alois Alzheimer in
1907 Course of disease -initially, some memory
loss (new memories and disorientation -relentles
sly progressive until one loses identity
29
Neuropathology in Alzheimers disease
30
Neurofibrillary tangles
Silver stain
Paired helical filaments
31
Formation of NFTs
32
Amyloid plaques
33
Formation of amyloid plaques
Amyloid precursor protein
34
Formation of amyloid plaques
35
Formation of amyloid plaques
36
In addition.
Massive loss of synapses in cortex
Mild
Moderate
Severe
37
Basal forebrain involvement
Nucleus basalis of Meynert
38
Causes
Largely unknown -Downs syndrome link -but
strongly inherited forms account for only small
proportion -plaques seen in wide variety of
disorders acquired by disease (encephalitis,
CJD) and accident (punch- drunk syndrome)
39
Treatments

• Cognitive enhancers
• -Acetylcholinesterase inhibitors to offset loss
  of cholinergic neurons
• NMDA antagonists
• -Memantine
• -idea here is that part of problem in AD is that
  chronic release of glutamate prevents NMDA
  receptors from working properly