FINAL QUESTIONS Flashcards
(30 cards)
1
Q
*Broadly describe some of the neuropsychological consequences of chronic cannabis use (Q30)
A
- Tolerance: typically pharmacodynamic (involving a combo of desensitization and down-regulation of CB1 receptors), evidence that desensitization can be reversed
- Dependence: 10% of cannabis users become dependent
- Withdrawal: absence of withdrawal symptoms in studies may have been due to the long elimination half-life of THC; involves lower dopamine VTA firing and increased CRF and cortisol release
2
Q
*Identify five acute psychological effects associated with typical recreational doses of inhaled cannabis (Q27)
A
- Pain perception: reduced unpleasantness of pain, but intensity of pain remains the same
- Visual selective attention: increase in reaction times, decrease in accuracy, reduced binocular depth inversion
- Auditory effects: improved rhythm perception
- Memory: all aspects of memory impaired but especially working memory
- Euphoria: dependent on the THC content
3
Q
*Identify some of the behavioural and physiological atypicalities observed in both CB1 and CB2 knockout mice (Q29)
A
- CB1 knockout mice lack four characteristic THC-induced effects: reduced locomotion, hypothermia, catalepsy, hypoalgesia
- CB1 knockouts do not show extinction of fear conditioned responses to auditory cues
- CB2 knockout mice exhibit hyperalgesia
- Hypothalamic effects are mediated by TRPV1, which also mediates LTD in the hippocampus
- TRPV1 is involved in thermal and pain regulation
4
Q
*Describe some of the unique features of endocannabinoid neurotransmission compared to other neurotransmitter systems (Q26)
A
- Too lipid soluble to be stored in vesicles because they would pass right through the vesicle membrane
- Instead of being stored in vesicles, they are made and released when needed
- Endocannabinoids are retrograde messengers at specific synapses in some brain regions (ie. hippocampus, cerebellum)
- After they are released, endocannabinoids are removed from the extracellular fluid by an uptake mechanism
- They can be metabolized by several different enzymes (ie. FAAH, MAGL)
5
Q
*Cannabis is becoming increasingly common in the treatment of some chronic pain disorders. Explain how the underlying neural circuitry for pain is modulated by the use of cannabis (Q28)
A
- CB1 receptor agonists directly decrease the firing rate of peripheral nociceptive neurons
- Spinal and thalamic neurons in the pain pathway are similarly affected by agonists
- Distinct central sites of anti-nociceptive action: PAG, RVM, A5 NE cells
6
Q
*Provide an account of the mechanisms of action for the psychoactive effects of cocaine (Q1)
A
- Different routes of administration produce different effects due to the time course of distribution
- Binds to membrane DA transporter and blocks the reuptake of the neurotransmitters
- Crosses the BBB because it is lipophilic
- Quickly broken down by blood and liver enzymes
- Half-life is typically 0.5-1.5 hours
- High affinity for SERT > DAT > NAT
- Low affinity for voltage-gated Na+ channels
7
Q
*Provide an account of the mechanisms of action for the psychoactive effects of amphetamines (Q2)
A
- 2 drug related actions: cause DA molecules to be released from inside vesicles at cytoplasm of nerve terminal and DA molecules transported outside of terminal by reversal of DAT
- Half-lives range from 7-30 hours
- Metabolites mostly excreted in urine
- Amphetamines and methamphetamines are indirect agonists of the catecholaminergic systems
- Releases catecholamine from nerve terminals
- At very high doses, amphetamines can act as MAO antagonists
- Reversal of DAT function is caused by phosphorylation through PKC
- Release of NE happens in both the brain and the sympathetic nervous system
8
Q
*Explain why amphetamines and other psychostimulants are used in the treatment of attention deficit disorders (Q3)
A
- Low doses of amphetamines produce calming effects in more than half of ADHD sufferers
- A single dose early in the day will benefit the child throughout the day because it is long-acting
- Abnormal prefrontal cortex activity is restored to near normal
- α2A and DA1 receptors are most implicated
- Enhancing catecholaminergic activity in the PFC has been suggested to be a crucial component in ADHD, and psychostimulants are capable of stimulating the release of and blocking the reuptake of catecholamines
9
Q
*Provide an account of the mechanisms of action for the psychoactive effects of nicotine (Q4)
A
- Typical cigarette contains between 6-11mg but only about one third of it reaches the bloodstream
- Enters the lungs on particles of hydrocarbon mixtures
- Smoking is the fastest and most efficient was of getting nicotine into the brain
- Half life is ~2 hours
- 70-80% metabolized to cotinine by CYP2A6 in the liver
- Mainly activates nicotinic acetylcholine receptor sites in the CNS, PNS, muscle junction
- High dose can lead to biphasic response
10
Q
*Provide an account of the mechanisms of action for the psychoactive effects of caffeine (Q5)
A
- Absorbed by the gastrointestinal tract within 30-60 minutes after consumption
- Stimulates calcium release within cells
- Absorption begins in the stomach but takes place mainly in the small intestine
- Plasma half-life is about 4 hours
- Converted in the liver to multiple metabolites
- Mostly excreted through urine
11
Q
*Broadly outline (or list) the neurophysiological components of anxiety and match each CNS component with a behavioural or physiological correlate (Q6)
A
- Lateral hypothalamus: sympathetic activation
- Dorsal motor nucleus of Vagus: parasympathetic activation
- Parabrachial nucleus: increased respiration
- VTA, LC, PPN: activation of DA, NE, and ACh
- Nucleus reticularis: increased reflexes
- Periaqueductal grey: cessation of behaviour
- Trigeminal and facial nuclei: mouth open and jaw movements
- Paraventricular nucleus of hypothalamus: ACTH release
12
Q
*Several neurotransmitters are thought to contribute to the experience of anxiety. Identify the ones discussed in lecture and for each one provide a one sentence summary about its contribution (Q7)
A
- CRF: prepares the organism for increased stress and utilization of energy
- Norepinephrine: involved in arousal and response to threats/novel situations, also improves memory formation for emotional events
- GABA: the GABAa receptor complex comprises a chloride channel that, when opened following GABA binding, allows chloride to enter the cell, causing hyper polarization
- Serotonin: 5HT agonists tend to be anxiolytic
- Dopamine: involved in fear and avoidance behaviour
13
Q
*Provide an account of how benzodiazepines function to treat anxiety (Q8)
A
- Differences in effect duration are largely dependent on method of biotransformation and depot binding
- Long-acting benzodiazepines can have half-lives of 60+ hours and/or have multi-step metabolism with bioactive metabolites
- Short-acting benzodiazepines are metabolized in a single step
- Benzodiazepines can have sedative-hypnotic and memory impairing effects
- Clinically useful for relief of worry and physiological signs of anxiety with little to no tolerance for anxiolytic effects
- They are advantageous because they have a high therapeutic index, lethal overdose is rare, no liver enzyme increases, and lower dependence/abuse
14
Q
*List five treatment options available for major depression and for each one provide a one sentence summary about how that option is supposed to work (Q10)
A
- MAOI: increases the amount of NT available for release; involves many side effects, but has an immediate effect on DA, NE, and 5HT synapses; antidepressant effects are the result of receptor regulation over time
- Tricyclic antidepressants: non-selective monoamine reuptake inhibitors, inhibition of reuptake prolongs the duration of transmitter action at the synapse; antidepressant effects are likely due to long term regulation, also block ACh, histamine, and α2 NE receptors
- Second generation antidepressants: not more effective than MAOIs or tricyclics but have less side effects, 5HT is complex and some side effects come from SSRIs; requires compensatory changes in neurons that occur over time
- Third generation antidepressants: comprise of CRF receptor antagonists, ketamine, galanin, etc.; ketamine is a dissociative anesthetic that has been shown to produce a rapid reduction in symptoms; galantines involved in mood disorders, cognitive performance, sleep, stress responses, etc.
- Electroconvulsive shock therapy: very safe and effective, causes a brief seizure in the brian, one of the fastest ways to relieve symptoms
15
Q
*There are five families of endogenous opioids (endorphins). For each, name either the family itself or the propeptide from which they are derived (Q12)
A
- Endorphins: derived from POMC
- Enkephalin: derived from proenkephalin
- Dynorphins: derived from prodynorphin
- Nociceptin/orphanin FQ: derived from pronociceptin/orphanin FQ
- endomorphin: unknown
16
Q
*Explain the role of endorphins and other opioids in the neurocircuitry of pain (Q13)
A
- Two distinct components: early pain and late pain
- Early pain is sensory and highly informative
- Late pain is an emotional and autonomic response
- Early pain activates contralateral primary somatosensory and bilateral secondary somatosensory cortices
- Late pain activates bilateral secondary somatosensory and anterior cingulate cortices
- Three ways opioids inhibit pain: through descending inhibition of spinal projection neurons, inhibition of excitatory interneurons, and modulation of inhibitory and excitatory opioid interneurons
17
Q
*Explain the pharmacological basis and rationale for the methadone maintenance program in treating opioid addiction (Q15)
A
- It is the best way to wean addicts off of opioids
- Produces a relief from the craving
- It’s the substitution of a strong short-lasting opioid for a weak long-lasting opioid
- Reduces withdrawal symptoms at a comfortable level
18
Q
*Describe some of the abnormalities of brain structure typically observed in individuals with schizophrenia (Q16)
A
- Reduction in grey matter volume
- Enlargement of lateral ventricles
- Reduced volume of basal ganglia, temporal lobe, and limbic regions
- More disorganized hippocampal cells
- Connectivity failures resulting from shrunken dendritic “trees”
- Some cortical layers are atrophied
- Many changes seem to be symptoms rather than causes
19
Q
*Briefly describe some of the evidence that implicates dopamine and glutamate dysregulation in the etiology of schizophrenia (Q17)
A
- Dopamine agonists can induce schizophrenia-like symptoms and amplify them in schizophrenics
- D2 antagonists are used as an effective treatment
- Low levels of glutamate may both increase mesolimbic and decrease mesocortical DA activity
- Glutamate involved in abnormal cognitive function and impaired neural connectivity
20
Q
*Describe what is meant by “broad-spectrum” antipsychotics and explain the rationale for their development in the treatment of schizophrenia (Q18)
A
- Molecules with complex receptor binding affinities
- Designed to target symptoms and side effects
- They block a wide range of receptors in addition to the D2 receptor
- Clozapine is an example of this
21
Q
*Describe the characteristic biological dysfunctions and treatment options associated with Alzheimer’s disease (Q19)
A
- Preceded by mild cognitive impairment
- Amyloid plaques of three forms: surrounded by axons/dendrites, diffuse depot of amyloid, dense core of amyloid
- Neurofibrillary tangles: tau proteins that make up microtubules can become abnormally phosphorylated and cause these tangles
- Seems to target cholinergic cells involved in cognition
- Two categories of treatment: cholinesterase inhibitors and NMDA antagonists
22
Q
*Describe the characteristic biological dysfunctions and treatment options associated with Parkinson’s disease (Q20)
A
- Mostly presents as a 4-6Hz resting tremor
- Most commonly observed as a loss of DA cells in the substantial nigra
- Later degeneration occurs in basal forebrain nucleus, amygdala, parahippocampal, etc.
- Treatment options include L-DOPA, MAOIs, DA agonists, Amantadine, Statin drugs
23
Q
*Describe the neurochemical underpinnings of the effects of psychedelic drugs (Q21)
A
- All psychedelic drugs act as agonists for the 5HT2A receptor, which is necessary but not sufficient for the psychedelic experience
- The mGlu2 receptor must be coactivated with 5HT2A in order to generate the psychedelic response
- 5HT21 and mGlu2 form a functional heterodimer in the cortex
- 5HT2A receptors mediate the subjective effects of indolamine and phenethylamine hallucinogens
24
Q
*Outline some of the psychological effects that are typically reported to be occasioned by the use of psychedelic drugs (Q22)
A
- Not linked to mental health problems or suicide
- Many subjective effects involve altered and/or mystical states of consciousness
- Frequently associated with ecstatic states
- Can devolve into states of anxiety and despair
- Visual perception: binocular rivalry, reduced tracking performance, reduced object completion, colour enhancement
- Increase in wakefulness
- Time distortion
- Enhanced suggestibility
- Enhanced emotional responses
- Reduced psychological distress
25
*Provide an account of the mechanisms of action for the psychoactive effects of ketamine (Q25)
- Stimulates DA release especially in the mesocortical pathway
- Antagonistic at the NMDA receptor but has affinities at several other receptors
- Potentiates GABAa
- Blocks LTP
- Induces catecholamine release
- Neurotoxic at high doses
26
*Identify some of the changes in brain activity that have been described from imaging studies of subjects under the influence of psilocybin. Relate these changes to one of the psychological effects of the drug (Q23)
- MEG study: decrease in frequency in differential brain areas
- Decrease in phase synchronization (ACC, PCC, parahippocampal)
- Decreases in anterior and posterior cingulate cortices
- Anterior cingulate cortex related to cognitive hierarchical goal setting and planning
- Posterior cingulate cortex related to default mode network (network of activity involved when you are not doing a task, i.e. daydreaming)
- Decreases in the thalamus and medial prefrontal cortex
27
*Broadly outline (or list) the neurobiological components of major depression and match each CNS component with a behavioural or physiological correlate (Q9)
- Glucocorticoid hypothesis: focuses on the stress-related abnormalities (elevated cortisol levels, abnormal secretion of CRF from the hypothalamus)
- Neurotrophic hypothesis: low BDNF may be responsible for the loss of dendritic branches in the hippocampus
28
*List all of the endogenous metabotropic opioid receptor subtypes, their associated G protein, and a distinguishing psychological correlate of agonism at each subtype (Q11)
* *G protein for all of them is Gi**
- Mu: role in feeding, reinforcement, homeostasis
- Delta: olfaction
- Kappa: regulating pain perception
- NOP-R: feeding, learning, movement, endocrine regulation
29
*Explain Himmelsbach’s model of opioid tolerance and withdrawal, including a physiological correlate (Q14)
- The nervous system adapts to disturbances caused by opioids by developing a tolerance
- Maintains homeostasis
- When the drug administration is suddenly stopped, the adaptive function of tolerance continues and overcompensates
- Tested this with morphine: it initially decreased production of cAMP, but after 2 days, levels of cAMP were equal to the control cells, after the drug was removed, concentration of cAMP went above control levels
30
*Describe two of the historical or currently proposed clinical applications of psychedelic drugs including their rationale (Q24)
- Early clinical uses included treatment for alcoholism and addiction, autism, and smoking
- MDMA was used in the late 70s and early 80s primarily by psychiatrists for couples counselling
- Recent interest in MDMA assisted psychotherapy for PTSD
- Psilocybin used for alcoholism, OCD, and death anxiety
