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136 Cards in this Set
- Front
- Back
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Which opioid receptor type preferentially binds narcotic opioids such as heroin and morphine? |
(mu) μ |
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What do all three of the opioid receptors have in common? They all _____. |
Are inhibitory metabotropic receptors |
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An example of a synthetic opioid is _____. |
Fentanyl |
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Overdose death from opioids is caused by ____. |
Respiratory depression |
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Which is NOT one of the three ways that opioids can produce inhibition at the neuronal level? |
Somatodendritic: enhanced activation of Cl- channels. |
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The half-life of nicotine is about ___ and that of caffeine is about ___.
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2 hours, 4 hours.
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Effects of Mu (μ) receptor activation:
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•Analgesia• Reward• Respiratory depression • Cough control• Vomiting |
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Effects of Delta (δ) receptor activation:
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•Analgesia •Reward•Cognitive function
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Effects of Kappa (κ) receptor activation:
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•Dysphoria •Hallucinations •Reduced pain perception
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The Mu (μ) receptor has a ____ affinity for morphine and other narcotic analgesics, which are ____ of the μ receptor.
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high, agonists
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The Mu (μ) receptor preferentially binds
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the endogenous endomorphins and (beta) β-endorphin.
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The Delta (δ) receptor preferentiallybinds
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endogenous enkephalins. |
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The Kappa (κ) receptor preferentially binds |
Endogenous dynorphin |
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“First” (early) pain pathway:
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the somatosensory cortex, transmitted via myelinated Aδ(delta) fibers
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“Second”(late) pain pathway:
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anterior cingulate cortex, transmitted by unmyelinatedC fibers |
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Rewarding (reinforcing) effect of opioids is associated with
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disinhibition of the mesolimbic dopamine system.
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Homeostasis:
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the active process of maintaining a physiological parameter constant. |
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Benefits of nicotine for Parkinson’s’s disease:
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•may increase dopamine in the basal ganglia. Evidence from epidemiological studies suggest a relationship between cigarette smoking and low risk of Parkinson's disease.
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Benefits of nicotine for Alzheimer’s:
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•nicotine patches increase memory, attention. |
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Benefits of nicotine for Schizophrenia:
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May reduce negative symptoms (apathy, withdrawal…) as well as cognitive deficits. Over 80% of schizophrenic individuals smoke. |
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The primary mechanism of caffeine’s action is the
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inhibition of adenosine receptors. This is what produces the stimulatory effectsof caffeine. |
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What are adenosine receptors?
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They are GPCR receptors that bind adenosine, which acts as a neurotransmitter in the CNS. - They can be either stimulatory orinhibitory. - Adenosine causes sleepiness, and caffeine blocks this effect. |
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Tea leaves contain significant amounts of both caffeine and a related compound called
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theophylline (which is Greek for “divine leaf”)
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Nicotine is more rewarding during adolescence. |
This may make adolescence a critical period of vulnerability to nicotine addiction. |
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Smoking and stress: |
Deprivation reversal model |
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Smoking started to decline in the US after |
Early studies linking smoking and cancer came out in 1950s First Surgeon General’s report on smoking in 1964. Anti smoking ads 1966-1970 followed by the Nonsmoker’s rights movement |
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Smoking was on the rise in the US during |
World War I (1914-1918) Great Depression End of World War II |
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Health effects of nicotine: |
According to NIDA, smoking kills an estimated 440,000 U.S. citizens each year—more than alcohol, cocaine, heroin, homicide, suicide, car accidents, fire, and AIDS combined.
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Therapeutics for smoking cessation |
Nicotine replacement (patch, gum, lozenge, inhaler). Lifetime success rate about 7%.
•Zyban (bupropion), an antidepressant marketed as Wellbutrin which was discovered to reduce smoking accidentally, is a NE and DA reuptake inhibitor and a nAChR antagonist.
•Chantix (varenicline), a nAChR partial agonist. |
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Drug diversion |
The use of prescription drugs for recreational purposes |
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Laudanum
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1680: First patent medicine containing opium was produced.
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Anxiety
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The anticipation of potential danger and is experienced as a feeling of worry or concern.
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Acute anxiety
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A normal, brief response to real-life situations such as the death of a loved one.
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Long-lasting or extreme levels of anxiety
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are maladaptive and can escalate.
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Three-component model of anxiety Bodily effects of anxiety |
Shallow breathing, pounding heart, tense muscles, digestive problems, autonomic emergency response, sleep disturbances, fatigue, and psychosomatic illness
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Three-component model of anxiety Ineffective behavior of anxiety |
Escape, avoidance, indecision, aggression, inflexible responses, poor judgment, inefficiency, and drug use |
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Three-component model of anxiety Upsetting thoughts |
Anger, fear, preoccupations, self-doubt, negative self-talk, repeated "danger" thoughts, and worry about body reactions and health |
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Generalized anxiety disorder (GAD):
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long-lasting symptoms of anxiety with noreal focus. •Constant worry, even over minor events. •Physical symptoms include muscle tension, agitation, poor concentration, irritability,and sleep disturbances. •Usually persists throughout life if untreated.
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Panic disorder
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the individual experiences an intense fear reaction without a threatening stimulus. This is accompanied by strong arousal of the sympathetic branch of the ANS. •Symptoms include pounding heart, chest pain, sweating, shortness of breath, faintness, choking, fear of dying, afeeling of impending doom. •can be induced in vulnerable individuals by lactic acid, yohimbine, and caffeine.
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Naloxone |
an opioid antagonist with a very high affinity for the mu opioid receptor. - It will displace opioid agonists, making it extremely useful for the treatment of overdoses (it can restore breathing).
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Suboxone |
A mixed mu agonist (bupenorphine) and antagonist (naloxone). - Much less bioavailability of naloxone when taken sublingually (the way it is meant to be taken) than if it is crushed and injected. - was designed to reduce diversion and abuse. |
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Kratom |
has multiple actions, one of which is a mu opioid receptor agonist. - is a plant that grows in SE Asia that has been used medicinally for pain and for treating symptoms of withdrawal from other opioids. - It has a number of alkaloids, one of which binds to and activates mu opioid receptors. |
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methadone |
The m receptor agonist which is used clinically for patients who want to withdraw from heroin. - It controls maintenance. - lessens the intensity of withdrawal, but individuals often stay on this type of maintenance for years. |
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Heroin is a “pro-drug” for morphine |
Heroin is very lipophilic, much more so than morphine. -Heroin has a low affinity for the m opioid receptor. - Once it enters the brain, it is quickly metabolized to morphine, which has a high affinity for the m opioid receptor. - In the USA, heroin is a schedule 1 drug. Morphine (and many other opioids) are Schedule 2.
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Model of the effects of opiates on mesolimbic dopaminergic cells |
Rewarding (reinforcing) effect of opioids is associated with disinhibition of the mesolimbic dopamine system. - Mu opioid receptors are on GABA terminals. - Inhibition of GABA = activation of DA neurons in the VTA. |
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Endogenous opioids |
Enkephalins Endorphines Dynorphins Endomorphins |
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Caffeine content of brewed coffee |
80 (40-110) |
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Caffeine content of Starbucks breakfast blend |
415 (300-564) |
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Caffeine content of tea |
27 (9-51) |
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Caffeine content of coca-cola |
49 |
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Caffeine content dark chocolate |
10-15 |
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Caffeine content in PowerBar Acticaf Performance Bar |
50/60-g bar |
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Caffeine content No-Doz Drug |
200 |
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The mesolimbic dopamine (DA) pathway from the VTA to the nucleus accumbens (NAcc) plays |
A key role in nicotine’s reinforcing effects |
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High-affinity nicotinic receptors located in the VTA stimulate |
the firing of dopaminergic neurons, which causes increased DA release in the NAcc |
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Nicotinic receptors are also found in the NAcc, where they contribute to |
nicotine reinforcement by modulating DA release from the mesolimbic nerve terminals |
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Nicotine effects on cognitive function |
Abstinent smokers given nicotine show enhanced performance on many kinds of cognitive and motor tasks, particularly those involving attentional demands. - There is support for the conclusion that nicotine has a positive influence on cognitive and motor functioning even in nonsmokers. - This analysis found statistically significant effects of nicotine on fine motor performance, and on accuracy and response latency in certain types of attentional and memory tasks. |
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Which opioid receptor type preferentially binds narcotic opioids such as heroin and morphine? |
(mu) μ |
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What do all three of the opioid receptors have in common? They all _____. |
Are inhibitory metabotropic receptors |
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An example of a synthetic opioid is _____. |
Fentanyl |
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Second (or late) pain, but not first (early) pain, involves the ____. |
Anterior cingulate cortex. |
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Effects of the mu (μ) receptor activation include all of the following EXCEPT which of these? a. Analgesia b. Hallucinations c. Reward d. Respiratory depression |
B. Hallucinations |
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During morphine withdrawal, levels of cAMP ____. |
Increase |
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Which of these is an anti-smoking drug that acts on the α 4β 2 nicotinic receptor but can cause severe psychiatric side effects? |
Chantix |
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Which of the following is an example of a semisynthetic opioid narcotic?
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Oxycodone |
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Which of the following is NOT an effect of moderate doses of caffeine? |
Feeling of euphoria. |
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Approximate amount of nicotine in a cigarette and the time course of smoking
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A typical cigarette contains 6 to 11 mg of nicotine. - Nicotine is absorbed by the lungs and reaches the brain in about 7 seconds. |
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Adverse effects of nicotine
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Smoking increases the risk for many life-threatening illnesses, including several kinds of can- cer, cardiovascular disease, and respiratory disease. - Smoking can also lead to other respiratory diseases such as emphysema and chronic bronchitis (together sometimes known as chronic obstructive pulmonary disease, or COPD). - Smokers are at increased risk for heart attack, stroke, and atherosclerosis, and evidence has been accumulating that long-term smokers suffer a decline in cognitive function over time compared with nonsmokers. - Smoking during pregnancy is the leading cause of low birth weight, which delays the infant’s development and puts her at risk for other complications. |
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Adverse effects of nicotine for never smokers
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Dizziness, headache, nausea |
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agoraphobia
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a fear and subsequent avoidance of public places. - Some become entirely unable to leave their homes. |
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Post-traumatic stress disorder(PTSD)
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can occur after traumatic events such as war, terrorist attacks, physical assault including rape, and natural disasters such as hurricanes. - The incidence of PTSD varies depending on the stressor. Estimates are about 4-16% of survivors of natural disasters, 30% of war veterans, 50% of people who have been raped, 50-75% of prisoners of war who have been tortured. |
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PTSD stats
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Reduced cortisol in patients with post-traumatic stress disorder (PTSD) - Children with parents that have PTSD have an increased risk of PTSD. - Low cortisol levels in PTSD patients may indicate a hypersensitive HPA axis negative feedback system. |
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Symptomsof PTSD
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include recurring nightmares or flashbacks of the traumatic event, avoidance of and heightened reactivity to reminders of the trauma, sleep disturbances, and emotional numbing. - Hippocampal atrophy was long thought to be a consequence of PTSD. |
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Twin study of hippocampal volume in PTSD
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More recently, twin studies suggest that reduced hippocampal volume may be a predictor of PTSD. - Identical twin pairs: twin with PTSD and one without. Both sets have similar-sized hippocampi. - Twin sets in which one had PTSD: both twins had smaller hippocampi. Having a small hippocampus predisposes to PTSD. |
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Obsessive-compulsive disorder
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OCD is characterized by persistent, intrusive, troublesome thoughts (obsessions) that the individual tries to resist. - These thoughts cause a great deal of anxiety and guilt, which the person attempts to relieve by repetitive rituals (compulsions). - appears to involve abnormalities of a neural circuit involving overactivation of the basal ganglia. - Treatment with SSRIs and cognitive behavioral therapy can both reduce this hyperactivity. In extreme cases, cingulotomy has been used. |
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Benzodiazepine swere developed in the
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1960’s to treat anxiety without the excessive sedation caused by barbiturates. - They are much safer than barbiturates because they have a lower incidence of tolerance, less abuse liability, and a greater therapeutic index. - They produce little respiratory depression, so lethal overdoses are rare. |
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Barbiturates and benzodiazepines both act on the _____, but in different ways.
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GABAA receptor
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Barbiturates prolong the duration
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of GABA-activated chloride channel opening and can directly open the channel without GABA, the likely reason for the lethality of these
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Benzodiazepines increase the number of
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of times the channel opens when GABA binds but has no effect without GABA.
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The amygdala coordinates components
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Of emotion, as it connects to many regions of the brain that regulate the expression of emotion. - The prefrontal cortex projects to the amygdala and other emotion-related brain regions and provides inhibitory control. - brain regions: lateral hypothalamus, locus coeruleus, |
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The amygdala coordinates components of emotion
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Physiological effects of activation of emotion-related brain regions - psychological effects are sympathetic activation, activation of DA, NE and ACh - cessation of behavior - ACTH (adrenocorticotropic hormone) release |
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The amygdala coordinates components of emotional response
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Increased heart rate and blood pressure, paleness pupil dilation - behavioral arousal and increased vigilance - freezing - glucocorticoid release |
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Corticotropin-releasing factor (CRF)
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can be both a hormone and a neurotransmitter. - In addition to stimulating ACTH release in the pituitary (a hormonal action), CRF is released as a neurotransmitter in emotion-related brain regions, especially the amygdala (a neurotransmitter action).
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The effects of early handling are related to the behavior of the mother.
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Some mother rats spend a lot of time licking, grooming, and nursing their pups. Others seem to ignore their pups. Highly nurtured rat pups tend to grow up to be calm adults, while rat pups who receive little nurturing tend to grow up to be anxious. - It turns out that the difference between a calm and an anxious rat is not genetic, it's epigenetic. The nurturing behavior of a mother rat during the first week of life shapes her pups' epigenomes. And the epigenetic pattern that mom establishes tends to stay put, even after the pups become adults. |
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Causes of stimulatory effects of caffeine |
fatigue-reducing effects - At high doses of caffeine, humans experience feelings of tension and anxiety. - caffeine increases our arousal, and positive subjective effects, including feelings of well-being, enhanced energy or vigor, increased alertness and ability to concentrate, self-confidence, increased work motivation, and enhanced sociability. - Caffeine is particularly effective in improving concentration in fatigued subjects and in the elderly. |
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Causes of adverse effects of caffeine |
there are now several studies showing that tolerance does develop to at least some of caffeine’s subjective effects as well as its ability to disrupt sleep - Chronic caffeine use also produces tolerance to the cardiovascular and respiratory effects of the drug |
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The nontoxic stimulatory effects of caffeine are primarily due to inactivation of _____ receptors.
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adenosine
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What do heroin and oxycodone have in common?
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- They were marketed as less addictive alternatives to morphine. - They bind to mu opioid receptors. |
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Nicotine can cause _____ and paradoxical ___ effects.
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increased heart rate; anxolytic
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Which is NOT one of the components of the Three-component model of anxiety?
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genetic predisposition
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A feeling of impending doom and fear of dying are symptoms of _____.
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panic attacks
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The periaqueductal gray area, one of the projection regions of the amygdala, can cause ____ behavior when activated, and activation of the locus coeruleus, another projection region of the amygdala, can cause ____.
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freezing, vigilance
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An example of a barbiturate is _____ and of a benzodiazepine is _____.
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pentobarbitol, diazepam
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The most prevalent of anxiety disorders is/are ___.
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specific phobias
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Brief daily handling of rat pups, in contrast to extended maternal separation, results in _____.
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decreased fearful behavior
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Typical antipsychotics act primarily by blocking ___.
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dopamine D2 receptors
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“Prodromal” symptoms of schizophrenia __.
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often occur during childhood
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The dopamine hypothesis of schizophrenia proposes that there is ___.
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a deficiency of dopamine in the prefrontal cortex - an excess of dopamine in the limbic system
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The “Rule of Thirds” relates to the proportion of individuals with schizophrenia who ___.
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respond differentially to drug therapy
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Tardive dyskinesia is a side effect of antipsychotic drugs and is characterized by ___.
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abnormal involuntary movements
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In the _____ type of schizophrenia, the person is extremely withdrawn, negative and isolated, and has marked psychomotor disturbances.
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catatonic
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prodromal
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early warning signs of schizophrenia |
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Mirsky and Duncan Model
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Interaction between Stress and Genetic Influence in developing schizophrenia |
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Dopamine imbalance
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dopamine deficiency in the prefrontal cortex (negative symptoms), excess dopamine in the limbic system (positive symptoms). |
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dopamine disruption in schizophrenia
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dopamine hypothesis |
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glutamate hypothesis
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glutamate hypofunction can cause opposite effects in the mesocortical and mesolimbic pathway. glutamate projections excite mesocortical DA neurons and inhibit mesolimbic DA neurons (via GABA interneurons). Hypofunction will produce opposite effects. |
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Which of these statements is not true of anxiety?
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Anxiety is always caused by a real-life stressor. |
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Brief maternal separation that occurs due to neonatal handling results in long-lasting alterations in the stress response of rat pups (they are more resilient to stress). What is the most likely reason for this?
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Increased maternal behavior |
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The brains of schizophrenic patients are characterized by _____.
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a. hypofrontality b. enlarged ventricles c. disorganized neurons in the hippocampus D. ALL OF THE ABOVE |
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Atypical antipsychotic medications act on _____ receptors.
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dopamine D2 and serotonin receptors |
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Glutamate _____ can cause ____ in the mesocortical and mesolimbic dopamine pathways.
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hypofunction, opposite effects |
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What are three pathologies in which there may be beneficial effects of nictotine?
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Parkinson's, Alzheimer's, Schizophrenia.
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What does adenosine do, and what is the action of caffeine on this system?
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Makes you sleepy; caffeine blocks adenosine receptors
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What are 3 adverse effects of nicotine in people who have never smoked?
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Dizziness, headache, nausea
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What is 'late' pain?
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slower than early pain; uses unmyelinated C fibers; cingulate cortex is involved
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What opioid is primarily responsible for the recent increase in overdose deaths?
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Fentanyl
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What happens if users inject Suboxone?
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The naloxone will be effective and will block mu-opioid receptors, so the bupenorphine will be ineffective.
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Give an example of a drug that can increase a vulnerable individual’s likelihood of having a panic attack.
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Caffeine, Yohimbe (also lactic acid)
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What is the Yerkes-Dodson inverted U?
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It shows that very low and very high levels of arousal can impair performance on a task and that moderate amounts of arousal are optimal.
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What did the twin study with pairs of identical twins, one with PTSD and one without, show? What does this suggest about PTSD?
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In the twin sets in which one had PTSD: both twins had smaller hippocampi. Having a small hippocampus predisposes to PTSD.
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Typical (first generation) antipsychotics are best at treating these symptoms.
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Positive symptoms.
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What is an example of a negative symptom?
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poverty of speech, flat or blunted affect, inappropriate emotional response
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Briefly describe the Mirsky and Duncan vulnerability-stress model of schizophrenia development.
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Personal factors and environmental factors can be either stressors or protectors, and they can interact to produce prodromal symptoms, and potentially schizophrenia. The more protectors and the fewer stressors, the less likely it is that schizophrenai will occur.
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If you drink a cup of coffee containing 100 mg of caffeine at 4:00 p.m., about how much caffeine will remain in your system at midnight?
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About 25 mg.
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What are 2 effects that activation of both mu and delta receptors can produce?
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Analgesia and reward.
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What does the Mirsky and Duncan model tell us?
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Genetic vulnerability interacts with life stress to influence the probability of developing schizophrenia
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According to Dr. Kirsch, placebo effects should be large in depression because they provide what? |
Hope. |
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Why is the no-treatment control important in finding placebo effects? |
Because of natural history, progression, regression to the mean, the patient might just get better over time. |
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About what percentage of the effects of SSRIs can be attributed to the placebo effect? |
This ranges from 25% to 80% depending on the study.
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The Freedom of information act allowed Kirsch et al to use data from what government agency? |
The Food and Drug Administration (FDA) |
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How is statistical significance different from clinical significance? |
Statistical significance means: is the effect due to something other than chance? Clinical significance means: how big is the effect (does it actually improve the patient’s quality of life)? |
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What were some of the criticisms of Kirsch’s work? |
The patients were not depressed enough, or they were too depressed. Sample size was too small. Everybody knows they work! They can’t all be that wrong. |
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What is the measure that was used in most of the studies cited? |
The Hamilton depression scale. |
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How do published data from studies funded by drug companies compare to those funded by competitors or independent funding sources? |
The effect sizes are much greater. |
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What are some of the health risks of antidepressants in different age groups (infants, adolescents, and elderly)? |
Suicidal thoughts (adolescents), stroke (elderly), neonatal abstinence syndrome. |
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What treatments, other than placebo, seem to be as effective for depression as antidepressant drugs? |
Exercise, psychotherapy, acupuncture. |
