1. Neurotransmitters Neuropeptides Amines Amino acids Opioid peptides
Enkephalins (ENK)
Endorphins (END)
Peptide Hormones
Oxytocin (Oxy)
Substance P
Cholecystokinin (CCK)
Vasopressin (ADH)
Neuropeptide Y (NPY)
Brain-derived Neurotrophic factor
Hypothalamic Releasing Hormones
GnRH
TRH
CRH
Lipids
Anandamide
Gases
Nitric Oxide (NO)
Amines
Quaternary amines
Acetylcholine (ACh)
Monoamines
Catecholamines
Epinephrine (EPI)
Norepinephrine (NE)
Dopamine (DA)
Indoleamines
Serotonin (5-HT)
Melatonin
Amino acids
Gamma-aminobutyric acid (GABA)
Glutamate (GLU)
Glycine
Histamine (HIST)

2. Catecholamine Synthesis
Psychopharmacology2e-Fig jpg

3. Noradrenergic (NE) System
Psychopharmacology2e-Fig jpg

4. Noradrenergic (NE) System

5. Noradrenergic Receptors
Alpha 1 receptors
Smooth muscle
Skin
GI tract
Kidney
brain
Alpha 2 receptors
Beta 1 receptors
Heart
kidneys
Beta 2 receptors
Lungs
Liver
uterus
Vascular smooth muscle
Skeletal muscle
Beta 3 receptors
Fat cells
Noradrenergic Receptors
All metabotropic
Psychopharmacology2e-Fig jpg

6. Beta Blockers
Cardia arrhythmias
Second Heart Attack
Hypertension

7. Noradrenergic Receptors
Psychopharmacology2e-Table jpg

8. Ascending Reticular Activating System (ARAS)
Arousal Center

9. Rats showed increased time awake after administration of small amounts of either an α1- or a β-adrenergic agonist
Psychopharmacology2e-Fig jpg

10. Psychopharmacology2e-Table jpg

11. Dopaminergic (DA) System 1 Mesolimbic*
Ventral Tegmental Area (VTA)

12. Dopaminergic (DA) System 2 Mesostriatal*
Basal Ganglia

13. Dopaminergic (DA) System

14. Dopaminergic Receptors
D1 receptors
D2 receptors
D3 receptors
D4 receptors
D5 receptors
Psychopharmacology2e-Fig jpg

15. D1 and D2 receptors
Psychopharmacology2e-Fig jpg

16. Dopaminergic Synapse Tyrosine Tyrosine Hydroxylase DOPA
Aromatic Amino Acid Decarboxylase
Dopamine Transporter
Vesicular Monoamine Transporter
D2 Autoreceptor
Psychopharmacology2e-Fig jpg

17. Psychopharmacology2e-Table jpg

18. Parkinson’s Disease
A chronic, progressive, neurodegenerative disorder.
Although there are genetic and environmental risk factors, a definitive cause has not yet been discovered.
Risk of PD increases with age, but an early-onset variant occurs before age 40.

19. Parkinson’s Disease Tremors at Rest Akinesia Bradykinesia
occurs when limbs are relaxed, and disappears with intentional movement
Akinesia
difficulty in initiating movement
Bradykinesia
slowing of movement in general
Parkinson’s Disease Dimentia
slow decay of brain function 19

20. Parkinson’s Disease Progression
Stage 1: Degeneration starts in the dorsal motor nucleus of the vagus and the anterior olfactory structures, resulting in loss of sense of smell Stage 2: Degeneration then moves to the raphe and locus coeruleus Stage 3: Degeneration of the substantia nigra, amygdala, and nucleus basalis. Motor symptoms begin at this stage Stage 4: Degeneration of temporal lobe mesocortex. Stage 5: Degeneration of the temporal lobe, sensory association, and premotor areas. Stage 6: Degeneration of the primary sensory function and motor areas. 20

21. Selective loss of pigmented dopaminergic cells occurs in the substantia nigra
Psychopharmacology2e-Fig jpg

22. Lewy bodies
Psychopharmacology2e-Fig jpg

23. Disease Progression
Psychopharmacology2e-Fig jpg

24. The effects of Parkinson’s disease on motor control pathways
Psychopharmacology2e-Fig jpg

25. Treatment Options
Levodopa (l-DOPA), a metabolite of the amino acid tyrosine, is the immediate precursor of DA in its metabolic pathway. Side effects include motor fluctuations and dyskinesias—unwanted movements like severe tics
Monoamine oxidase inhibitors (MAOIs) prevent breakdown of DA, NE, and EPI.
Catechol-O-methyltransferase (COMT) inhibitors prevent breakdown of DA in the synapse but are given only as adjuncts to l-DOPA.
DA receptor agonists with longer half-lives than l-DOPA, and different side effects, including impulse control disorders, such as compulsive gambling.
The drug amantadine (Symmetrel) as monotherapy or to decrease dyskinesias related to l-DOPA. It is an NMDA receptor antagonist.
Statin drugs for lowering cholesterol may reduce the risk of developing PD by improving heart health and increasing anti-inflammatory effects. DA receptors are up-regulated by statin therapy. 25

26. Deep Brain Stimulation

27. Schizophrenia Onset can be slow or sudden Typically exists chronically
Affects ~1% of population
Diagnosis must have at least two symptoms for more that 1 month

28. Schizophrenia Symptoms
Positive Symptoms (abnormal states)
hallucinations (auditory, visual)
delusions (grandeur, persecution)
Negative Symptoms (insufficient functioning)
avolition (inability to initiate/persist in activities)
alogia (absence of speech)
anhedonia (inability to experience pleasure)
affective flattening (flat emotional response)
Disorganized Symptoms
inappropriate affect (laughing/crying at the wrong times)
disorganized speech (illogical, rambling, tangential)
disorganized behavior (catatonia, agitation/immobility)

29. Schizophrenia Subtypes
Paranoid Type
hallucinations
delusions
Catatonic Type
unusual motor responses
remaining in a fixed position
excessive activity or rigidity
echoing words or movements of others
Disorganized Type
speech problems
behavior problems
flat or inappropriate affect

30. Schizophrenia and Gender

31. Schizophreni Genetic Risk by Relatedness
The Evidence:
Family History
Twin Studies
monozygotic (50%)
same handed (92%)
dizygotic (15%)
both are carriers
Adopted Children
more like bioparents
Single Gene?
Probably not

32. Brain Structure Abnormalities Increased Lateral Ventricles

33. Brain Structure Abnormalities Reduced Hippocampus and Amygdala
Affected
Affected
Normal

34. Cortical gray matter loss
During adolescence, a period of significant brain development, excessive synaptic pruning can result in loss of cortical gray matter.
Psychopharmacology2e-Fig jpg

35. Brain Structure Abnormalities Hippocampal Pyramidal Cell Disorganization
Reelin is a glycoprotein secreted by neurons, that guides neuron positioning during fetal brain development.

36. Brain Structure Abnormalities Atypical Frontal Lobe Functioning
Evidence:
smaller forebrain
smaller cerebral cortex
smaller dorsolateral prefrontal cortex
fewer cortical neurons
smaller cortical neurons
abnormal neuronal development
neurons remain in white matter
fail to arrange in neat order
abnormal CAMs
less metabolic activity
hypofrontality
failure to increase activity following task
abnormal EEGs

37. Relevant Neural Pathways
Mesolimbic pathway
affects positive symptoms.
Mesocortical pathway
cognitive and negative symptoms.
Nigrostriatal pathway
motor side effects.
Tuberohypophyseal pathway
regulates pituitary hormone secretion; neuroendocrine effects. 37

38. Etiology of Schizophrenia
Psychopharmacology2e-Fig jpg

39. Neurobehavioral Hypothesis
Maternal/Fetal Evidence:
extensive maternal bleeding
prolonged labor
delivery complications
low birth weight
low head circumference
body length:body weight
multiparity
Anectodal Evidence
Dutch births during WWII
Season of birth effect
higher for winter pregnancies
parallel with virus exposure

40. Dopamine Hypothesis of Schizophrenia
Abnormal levels of Dopamine lead to the schizophrenic symptoms
1. Amphetamine Psychosis
Chronic users develop schizophrenic symptoms
paranoia, delusions of persecution, auditory hallucinations
Amphetamine exacerbates schizophrenic symptoms
Amphetamines promote the release of catelcholamines
particularly dopamine
2. Antipsychotic Drugs
chlorapromazine is a dopamine antagonist and antipsychotic
block specifically D2 and D4 receptors in the limbic system
effectiveness is related to magnitude of blockade
3. Parkinson’s Disease
some patients receiving L-dopa become psychotic
some schizophrenic patients on antipsychotics develop Parkinson’s symptoms

41. Hypoglutamate Hypothesis
Inadequate glutamate may explain the apparent increase in mesolimbic DA and decrease in PFC.
Descending glutamatergic neurons influence both DA pathways.
Psychopharmacology2e-Fig R.jpg

42. Treatment options
Neuroleptic is an older term for antipsychotic drugs. There are many of these drugs, and none are consistently more effective than the others. An individual may respond better to one drug than to another; several may have to be tested to find the one that is most effective. The classic antipsychotic drugs are phenothiazines and butyrophenones Negative and Cognitive symptoms are more resistant to treatment. Antipsychotic drugs block D2 receptors. A strong correlation exists between ability of a drug to displace a radio-labeled ligand on DA receptors and average clinical daily dose required. The drugs also bind to other receptors, but there is no clear relationship between clinical effectiveness and binding to serotonin, α-adrenergic, histamine, or D1 receptors. 42

43. Correlation between antipsychotic drug binding to neurotransmitter receptors and clinical effectiveness
Chlorpromazine (Thorazine) first drug to find positive effects
Strong Correlation with DA 2 receptor blockers
Psychopharmacology2e-Fig R.jpg