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Questions and Answers
What effect does LSD have on raphe neurons?
What effect does LSD have on raphe neurons?
Which receptor does PCP interact with as a non-competitive antagonist?
Which receptor does PCP interact with as a non-competitive antagonist?
Which condition was PCP withdrawn from clinical use due to?
Which condition was PCP withdrawn from clinical use due to?
What effect does PCP have on altered body perception?
What effect does PCP have on altered body perception?
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In which countries can psychiatrists prescribe psilocybin for psychedelic-assisted psychotherapy as of July 2023?
In which countries can psychiatrists prescribe psilocybin for psychedelic-assisted psychotherapy as of July 2023?
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What does PCP intoxication often exacerbate in patients?
What does PCP intoxication often exacerbate in patients?
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Which type of drugs have both LSD and PCP been used to model in animal studies?
Which type of drugs have both LSD and PCP been used to model in animal studies?
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What additional effect does LSD have on layer V pyramidal neurons?
What additional effect does LSD have on layer V pyramidal neurons?
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Which of the following is a defining feature of addiction?
Which of the following is a defining feature of addiction?
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What role does the limbic system play in addiction?
What role does the limbic system play in addiction?
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What is one consequence of the withdrawal syndrome?
What is one consequence of the withdrawal syndrome?
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Which area of the brain is primarily associated with rewarding stimulation?
Which area of the brain is primarily associated with rewarding stimulation?
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What is a primary function of the reward and punishment systems in the brain?
What is a primary function of the reward and punishment systems in the brain?
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Which of the following statements about self-stimulation behavior in experiments is true?
Which of the following statements about self-stimulation behavior in experiments is true?
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What is a common psychological effect of addictive behaviors?
What is a common psychological effect of addictive behaviors?
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Which of the following terms is associated with the phenomenon observed in neural circuits relating to food and addictive drugs?
Which of the following terms is associated with the phenomenon observed in neural circuits relating to food and addictive drugs?
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Which neurotransmitter axons are NOT found in the medial forebrain bundle?
Which neurotransmitter axons are NOT found in the medial forebrain bundle?
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What effect does spiroperidol have on reinforcement?
What effect does spiroperidol have on reinforcement?
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What brain area do dopamine axons in the medial forebrain bundle primarily project to?
What brain area do dopamine axons in the medial forebrain bundle primarily project to?
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Which of the following is NOT an effect of cocaine?
Which of the following is NOT an effect of cocaine?
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Cocaine affects neurotransmission by blocking which type of transporter?
Cocaine affects neurotransmission by blocking which type of transporter?
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In what way can optogenetic stimulation of dopamine neurons influence behavior?
In what way can optogenetic stimulation of dopamine neurons influence behavior?
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Which of the following statements about cocaine's effects on catecholamines is accurate?
Which of the following statements about cocaine's effects on catecholamines is accurate?
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What is a major risk associated with high doses of cocaine?
What is a major risk associated with high doses of cocaine?
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What was observed in mice with DA transporter knockout when administered cocaine?
What was observed in mice with DA transporter knockout when administered cocaine?
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What role does the F105 region play in cocaine-insensitive DA transporter knock-in mice?
What role does the F105 region play in cocaine-insensitive DA transporter knock-in mice?
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What was the result of using PET imaging to measure D2 receptor density in cocaine abusers?
What was the result of using PET imaging to measure D2 receptor density in cocaine abusers?
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Which of the following statements is true regarding the effects of cocaine on mutant DAT knock-in mice?
Which of the following statements is true regarding the effects of cocaine on mutant DAT knock-in mice?
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What adaptation occurs in the reward system of chronic cocaine users?
What adaptation occurs in the reward system of chronic cocaine users?
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What type of behavioral change is observed when animals develop conditioned place preference (CPP) to cocaine?
What type of behavioral change is observed when animals develop conditioned place preference (CPP) to cocaine?
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What was a significant finding regarding D2 receptors in individuals after detoxification from cocaine use?
What was a significant finding regarding D2 receptors in individuals after detoxification from cocaine use?
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Which of the following best describes the effect of cocaine on the locomotor activity of mice with DA transporter knockout?
Which of the following best describes the effect of cocaine on the locomotor activity of mice with DA transporter knockout?
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Study Notes
Neuropharmacology of CNS disorders - Psychoactive Drugs
- Psychoactive drugs affect the central nervous system (CNS).
- LSD decreases firing rate of raphe neurons, increases locus coeruleus activity, and increases activity of layer V pyramidal neurons in the cortex, leading to expanded primary visual cortex functional connectivity.
- Phencyclidine (PCP) is a dissociative anesthetic. It is in the same class as ketamine. PCP causes a catatonic-like state without muscle relaxation. It was removed from clinical use in 1965 due to emergence phenomena.
- Luby et al (1959) found that PCP in sub-anaesthetic doses in patients caused altered body image ("my arms and legs feel distant"), feelings of isolation, cognitive disorganization, drowsiness and apathy, negativism or hostility, euphoria and inebriation, and hypnagogic (dreamlike) states. It exacerbated symptoms in psychotic patients.
- PCP's effects on perception are linked to modulation of NAdr release by sigma opiate receptors, and antagonism of NMDA glutamate receptors.
Psychotomimetic Drugs
- Phencyclidine (PCP) is a dissociative anesthetic; affects the same receptors as ketamine.
- PCP causes a catatonic-like state without muscle relaxation.
- It was removed from clinical use in 1965 due to emergence phenomena.
Psychedelics in Disease Modeling
- LSD and PCP have been used in animal studies as drug-induced models for schizophrenia.
- Animal models used to study schizophrenia include: pharmacological models (MK-801, PCP, ketamine, amphetamine); neurodevelopmental models (MIA model, MAM model); myelin-related abnormalities (cuprizone model); and genetic models (DISC1, Dysbindin, Reelin, NRG1-ERBB).
Psychoactive Drugs and Treatment
- In Australia and New Zealand, since July 1, 2023, psychiatrists can prescribe products containing psilocybin for psychedelic-assisted psychotherapy in treatment-resistant depression.
Addiction
- Addiction is a persistent disorder of brain function characterized by compulsive drug use despite serious consequences.
- Features include compulsion to take the drug, tolerance (decreased response to repeated administration), and withdrawal syndrome (opposite effects to those experienced in presence of drug).
- Physical and psychological dependence can occur.
Addiction and the Limbic System
- Psychoactive drugs with abuse potential commonly affect the limbic system, including the amygdala, ventral tegmental area, and nucleus accumbens.
Addiction and Reward
- Reward, a pleasurable experience, is vital for survival.
- Behavioral selection relies on reward and punishment systems. These systems are essential for motivation and avoidance.
- Inappropriate activation of reward systems underlies addictive behavior.
A Psychological Framework for Reward and Addiction
- A reinforcing system detects stimulus (food, addictive drugs).
- It creates reinforcing stimuli and influences behavior like eating.
- A neural circuit that monitors and controls behavior.
Where are the Reward Centres in the Brain?
- James Olds and Peter Milner (1954) discovered reward centers in the brain using self-stimulation in rats.
- Stimulation in the septal area (medial forebrain bundle) led to frequent and prolonged self-stimulation.
What are the Reward Pathways in the Brain?
- The medial forebrain bundle contains axons originating in the midbrain/medulla and innervating brain regions.
- Axons include 5-HT from raphe neurons, noradrenergic axons from locus coeruleus neurons, and dopaminergic axons from ventral tegmental area.
- Dopamine pathways, specifically those in the medial forebrain bundle projecting to the nucleus accumbens, are crucial for reinforcement.
Cocaine
- Cocaine is a stimulant and local anesthetic, acting through blockage of voltage-gated sodium channels.
- Cocaine causes euphoria, appetite suppression, and can lead to tremors, convulsions, and CNS depression in higher doses. It may trigger psychosis in susceptible individuals.
- Cocaine's addictive properties provide insight into the biochemical basis of motivation and reward.
- Cocaine blocks dopamine transporters, which prevent the recycling of catecholamines and increases their synaptic levels.
Cocaine and Reinforcement
- Cocaine binds to monoamine transporters, including dopamine transporters.
- Mice lacking dopamine transporters exhibit elevated dopamine and increased locomotor activity; cocaine is less reinforcing in these mice, showing that dopamine systems are partly involved in reinforcement.
- Other molecules can also impact cocaine reinforcement. Cocaine-insensitive dopamine transporter knock-in mice do not have elevated extracellular dopamine or increased locomotion when given cocaine. There are different pathways and actions to consider.
Cocaine and Dopamine in Humans
- PET imaging with 11C-raclopride shows downregulation of D2 receptors in cocaine abusers. This reduction in D2 receptors persists after detoxification.
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