NANCY LONG SIEBER, PH.D. SEPT. 13, 2010 A bit about lupus and then Neuropathophysiology I

The arrow labeled "axon" is pointing directly at the initial segment. EPSPs and IPSPs are integrated at a site at the base of the axon called the initial segment (also known as the axon hillock).

Major Neurotransmitters Involved in Mood Regulation Norepinephrine Serotonin Dopamine

Depression

Drugs that treat depression Monoamine oxidase inhibitors (MAOIs) – block the enzyme that breaks down norepinephrine and serotonin Selective serotonin reuptake inhibitors (SSRIs) – block reuptake of serotonin by the presynaptic neuron. Eg: Prozac Serotonin-Norepinephrine reuptake inhibitors – block reuptake of both serotonin and norepinephrine. Some also block dopamine reuptake. Eg: Wellbutrin

While studying modern antidepressant drugs, researchers identified a treatment that worked 75% as well as the drugs under consideration, with no side effects.

It was the placebo.

The placebo effect is greatest on conditions that respond to the body’s own biochemicals, such as endogenous opioids and dopamine. Placebos sometimes work for: Hypertension Pain Parkinson’s disease Psoriasis Rheumatoid arthritis Ulcers Placebos do not work for: Atherosclerosis Cancer Growth-hormone deficiency High cholesterol Infertility Obsessive-compulsive disorder Newsweek 2/8/10 Sharon Begley “The Placebo Effect”

Current thoughts on antidepressants Antidepressants appear to be most effective for severe depression and chronic mild depression In mild to moderate depression, it is difficult to distinguish between drug effect and placebo effect. Drugs work best when combined with psychotherapy.

Bipolar Disorder Characterized by over activity of the amygdala and under activity of the prefrontal cortex

Diagnosed with bipolar disorder and attention deficit disorder at age 2. Died at age 4 of an overdose of prescription drugs used to treat these conditions. Is it better to diagnose and treat these conditions early, or is the risk of over- diagnosing and over-treating too great? How can we assure that parents don’t misuse these powerful drugs? Rebecca Riley How common is bipolar in children?

Dopamine Parkinson’s disease is associated with a loss of dopamine-producing neurons in the basal ganglia, which is involved in movement. Schizophrenia is associated with an excess of dopaminergic transmission.

The art of Louis Wain ( ) Throughout his career, Wain painted pictures of cats.

At the age of 57, Wain developed schizophrenia. The disease is reflected in his art:

Dopamine also helps regulate mood. Central to our feeling of pleasure and reward. Dopamine is also associated with motivation and memory. Addictive drugs and behaviors involve dopamine pathways.

Drugs and Dopamine All addictions are thought to involve dopamine – it provides the drive to repeat pleasurable behaviors eg: smoking, drinking, shopping, etc. Some drugs directly alter dopamine neurotransmission –Methamphetamine causes the release of large amounts of dopamine –Cocaine blocks reuptake of dopamine at the synapse

Methamphetamine use affects the entire body

Cocaine blocks dopamine reuptake – results in feelings of euphoria

Dopamine and Addiction Dopamine is made in the ventral tegmental area (VTA), and is released in the nucleus accumbens, the pleasure center.

Methamphetamine use causes permanent damage to the brain

How to treat addiction? Detoxification – safely withdraw from drug Rehabilitation – slow process of dealing with psychological as well as physical addiction Medications used: –Safer forms of drugs that act on the same receptors as the drug of abuse. Eg: nicotine patch, methadone –Drugs that block the effect of drug, or that cause illness if drug is used. Eg: Antabuse for alcohol. –Certain antidepressants also help. Eg: Wellbutrin

Alcohol Consumption Per Capita

Source: World Health Organization

How to treat addiction? Detoxification – safely withdraw from drug Rehabilitation – slow process of dealing with psychological as well as physical addiction. Medications used: –Safer forms of drugs that act on the same receptors as the drug of abuse. Eg: nicotine patch, methadone –Drugs that block the effect of drug, or that cause illness if drug is used. Eg: Antabuse for alcohol. –Certain antidepressants also help. Eg: Wellbutrin

Major Neurotransmitters Small Molecules Neuropeptides Acetylcholine Nitric Oxide Biogenic Amines Epinephrine Norepineprine Dopamine Serotonin Histamine Amino Acids Glutamate  Aminobutyric Acid (GABA) Glycine Aspartate Homocysteine Taurine Nucleotides Adenosine Adenosine triphosphate Hypothalamic Releasing Hormones Corticotrophic Releasing Hormone Growth Hormone Releasing Hormone Thyrotrophin Releasing Hormone Pituitary Peptides ß endorphins Oxytoxin Vasopressin Adrenocorticotropic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Growth Hormone Gastrointestinal Peptides Secretin Substance P Insulin Gastrin Neurotensin Somatostatin Cholecystokinin Others Angiotensin Bradykinin Neuropeptide Y Calcitonin