Final Exam

Question 1

what is ibogaine?

Answer 1

ibogaine is a psychoactive indole alkaloid derived from the root bark of the African shrub, ingestion can lead to intense visions with closed eyes like a waking dream, accompanied by a vivid recall of autobiographical visual memories, has a potential for therapeutic use but is cardiotoxic and cause hallucinations that can last more than 24 hours

Question 2

what is the therapeutic effect of ibogaine?

Answer 2

can alter addiction-related circuitry by promoting neural plasticity, TBG (a drug that is structurally similar to ibogaine) reduced the hallucinogenic effects of LSD (as measured by head twitch response)

Question 3

why is ketamine better than PCP?

Answer 3

shorter duration of action, reduced mind-altering effects, maintenance of protective airway reflexes, provided both analgesia and anesthesia, strong safety profile with respiratory stability

Question 4

what is the mechanism of ketamine?

Answer 4

anesthesia effects: acts as a non-competetive NMDAR antagonist, interferes with pain signal transmission in the spinal cord and inhibitis nitric oxide synthase (an enzyme that produces nitric oxide) which is important for pain signaling and consciousness
ion channels: ketamine can also block voltage-sensitive calcium channels which reduces the release of pain signaling NTs, ketamine blocks sodium channels which hyperpolarizes nerve cells

Question 5

what are the antidepressent effects of ketamine?

Answer 5

inhibits the reuptake of NE and serotonin, has been found that a single dose of intravenous ketamine produced rapid antidepressant effects in patients with MDD

Question 6

how does racemic vs R and S configuration ketamine differ?

Answer 6

racemic: equal quantities of R and S enantiomers are marketed as an anesthetic agent for diagnostic and surgical procedure
S: has higher affinity for NMDAR compared to equivalent doses of R and racemic ketamine, also has lower side effects, effective for 50% of patients with treatment resistant depression
R: lower NMDAR affinity and is not used as a clinical drug

Question 7

how does ketamine work on NMDAR?

Answer 7

NMDAR is tetrameric ion channel composed of four subunits that form a pore permeable to calcium, sodium, and potassium, when the membrane is depolarized the magnesium block in removed and calcium can enter the cell, ketamine binds inside the NMDAR when it is open which blocks further calcium influx, S ketamine works in the same way but does it more frequently

Question 8

how do ketamine and esketamine exert their antidepressent effects?

Answer 8

the initial action begins with NMDAR antagonism on GABAergic inhibitory interneurons which results in enhanced glutamate release into the synaptic cleft leading to BDNF release and more synaptic spine growth

Question 9

what does GluN2A knockout result in?

Answer 9

NR2A knockout mice showed reduced anxiety-like behaviors across multiple tests, the NR2A knockout mice displayed antidepressant-like behaviors

Question 10

where is the brain does ketamine exert antidepressant effects?

Answer 10

mPFC: ketamine acts on NMDAR on GABA interneurons which disinhibits pyramidal cells, enhanced synaptic connectivity and dendritic spine growth in mPFC
hippocampus: ketamine increases BDNF levels in this region, enhanced plasticity and structural changes (restores stress-induced synaptic deficits)
lateral habenula: ketamine blocks abnormal bursting activity in this anti-reward center, reduced activity here helps normalize downstream monoamine signaling
brainstem monoamine centers: ketamines effects on DR (serotonin) and VTA (dopamine) restores normal monoamine signaling

Question 11

how does ketamine alter brain connectivity?

Answer 11

MDD patients showed reduced connectivity in PFC compared to healthy controls, ketamine increases connectivity in the PFC and the number of brain regions with abnormal connectivity decreased dramatically (connectivity increased specifically in the lateral PFC, caudate and insula)

Question 12

how does ketamine alter the lateral habenula?

Answer 12

ketamine blocks NMDAR-dependent burst firing in the LH, this disinhibits downstream monoaminergic reward centers, reversing depression-like behaviors in animal models, LH bursts were shown to drive depression-like behavior, which ketamine reversed

Question 13

what is the circumplex model of emotions?

Answer 13

valence (positive or negative) and arousal (high or low) are used to measure emotions with opposite emotions being on opposite poles for valence and activation

Question 14

what was Charles Darwins theory of emotion?

Answer 14

he believed that animal emotions are homologs for human emotions and that there are a set of basic emotions that present across species

Question 15

what is the James-Lange theory of emotion?

Answer 15

emotions occur as a response to a specific physiological reaction (i feel afraid because my heart is pounding, i feel sad because i cry)

Question 16

what is the Cannon-Bard theory of emotion?

Answer 16

they observed that despite severing connections between emotional responses and physiological responses animals still had normal emotional responses, from this they concluded that emotions and physiological responses occur simultaneously (my heart pounds and i feel afraid)

Question 17

what is the Schachter-Singer theory of emotion?

Answer 17

we must label the physiological response in order to generate an emotion, individual perception and thoughts about a stimulus can influence the type of emotion (my pounding heart means i’m afraid because i interpret the situation as dangerous)

Question 18

what theory of emotion is most supported by scientific evidence?

Answer 18

James-Lange theory is most closely supported, Antonio Damasio proved that each basic emotion produces a distinct pattern of neuronal reponse and physiological changes that occur before they are interpreted as an emotion

Question 19

what is the Yerkes-Dodson law?

Answer 19

the optimal amount of arousal for performance is an inverted U-shaped curve where too little arousal leads to poor performance (boredom, lack of motivation) but too much arousal leads to poor performance as well (stress, anxiety)

Question 20

what is the ‘feeling’ stream/downstream path of the Papez circuit?

Answer 20

represents the rapid generation of emotional states and responses
thalamus -> hypothalamus -> anterior thalamus -> cingulate cortex

Question 21

what is the ‘thinking’ stream /upstream path of the Papez circuit?

Answer 21

represents the analysis of sensory information and formation of thought and memories
thalamus -> sensory cortex -> cingulate cortex -> hippocampus -> hypothalamus

Question 22

what makes up the limbic system and what does it do?

Answer 22

limbic system regulates emotions and social behaviors as well as memory formation and stress response and is made up of the hippocampal formation, thalamus, hypothalamus, cingulate cortex, amygdala and prefrontal cortex

Question 23

what are the sub-areas of the amygdala and what do they contain?

Answer 23

basolateral amygdala (BLA): cortex-like structure, 80% glutamatergic, 20% GABAergic interneurons, recieves input from sensory systems and allows them to pass through
central amygdala (CEA): striatum-like structure, mostly GABAergic neurons that project to other areas of the brain to mediate defensive behaviors, output region for the expression of innate emotional responses and their physiological processes

Question 24

how does the infralimbic and prelimbic cortexes respond to fear and drug-seeking?

Answer 24

IL: decreases fear and drug seeking (increases extinction of fear by inhibiting reconsolidation of memories)
PL: increases fear and drug seeking

Question 25

who is patient SM?

Answer 25

she has Urbach-Wiethe disease, a rare genetic disorder that caused bilateral calcification and atrophy of her amygdala, which resulted in exclusive and complete bilateral amygdala destruction since late childhood, as a result she has trouble recognizing fearful expressions, identifying how intense they are, and drawing fearful faces from memory

Question 26

what role do the amygdala and hypothalamus play in anger?

Answer 26

lesioning of the amygdala or stimulation has been used to treat severe, refractory aggression in some patients, stimulation of the hypothalamus has been shown to induce sham rage

Question 27

how do the lateral and anterior hypothalamus alter the rage response?

Answer 27

anterior: stimulation of anterior hypothalamus produces sham rage lateral: stimulation of the lateral hypothalamus produces true rage

Question 28

what role does dopamine play in social isolation/sadness?

Answer 28

optogenetic activation of DA neurons in a social context promotes social interaction while activating these neurons in the absence of a social conspecific is aversive, DR DA neurons projecting to the CeA promote sociality, while those projecting to the posterior BLA regulate negative affective state

Question 29

what four brain regions play a role in fear learning?

Answer 29

amygdala: the amygdala processes and stores emotional aspects of traumatic memories prefrontal cortex: the prefrontal cortex regulates emotional responses and can modulate fear memories in the amygdala hippocampus: the hippocampus encodes contextual information and supports memory consolidation and retrieval infralimbic prefrontal cortex: plays a role in extinction learning by inhibiting reconsolidation of memories

Question 30

what is the monoamine hypothesis of depression?

Answer 30

the monoamine systems of serotonin, noradrenaline, and dopamine are involved, low activity of at least one of these neurotransmitters is responsible for depression

Question 31

what are the major pathways of the dopaminergic system?

Answer 31

mesolimbic: VTA to nucleus accumbens nigrostriatal: substantia nigra to dorsal striatum/basal ganglia mesocortical: VTA to PFC

Question 32

where do serotonin neurons project and what behaviors do they regulate?

Answer 32

5HT neurons are in the raphe nucleus and project to the basal ganglia to control movement, obsessions, and compulsions while projections to the limbic area are involved in regulating anxiety and panic and projections to the hypothalamus regulate appetite and eating behavior

Question 33

where do norepinephrine neurons project and what behaviors do they regulate?

Answer 33

NE cell bodies are located in the locus coeruleus, in patients with depression low noradrenaline activity is associated with decreased alertness, low energy, inattention, loss of interest, concentration difficulties, and cognitive deficits

Question 34

how do monoamine oxidase inhibitors work?

Answer 34

MAOI bind to and inhibit MAOA in synapses from degrading 5HT and NE MAOI bind to and inhibit MAOB in synapses from degrading dopamine

Question 35

what are the 5 actions of tricyclic antidepressants (TCAs)?

Answer 35

SRI: block the reuptake of 5HT by blocking SERT NRI: block the reuptake of NE by blocking NET alpha: block a1 adrenergic receptors H1: block histamine receptors M1: block muscarinic cholinergic receptors

Question 36

how do selective serotonin reuptake inhibitors (SSRIs) work?

Answer 36

blocks SERT so that it cannot reuptake serotonin from the synapse, selective because they only block reuptake pumps for serotonin

Question 37

how do norepinephrine and dopamine reuptake blockers (NDRIs) work?

Answer 37

blocks DAT or NET so that dopamine and NE are stuck in the synapse

Question 38

how do noradrenergic and specific serotonergic antidepressants (NaSSAs) work?

Answer 38

acts as an antagonists to the alpha 2 receptors as well as blocking three kinds of serotonin receptors and histamine receptors, prevents the negative feedback effect of synaptic NE on 5HT (alpha receptors are autoreceptors on the presynaptic cell, by blocking NE from binding to the alpha receptors it stops them from inhibiting the release of 5HT and NE from the presynapse)

Question 39

what does inescapable shock do to the brain?

Answer 39

inescapable shock induces a strong activation of the DR serotonin neurons which leads to an acute release of 5HT in the amygdala, dorsal PAG, and nucleus accumbens, also induces a long-lasting desensitization of 5HT autoreceptors in the DR

Question 40

what is general adaptation syndrome (GAS)?

Answer 40

a foundational theory that describes how the body responds to prolonged exposure to stressors, contains an alarm stage, resistance stage, and exhaustion stage, where the bodies ability to withstand the effects of stress increase during alarm, are maintained throughout resistance, and then decreased throughout exhaustion

Question 41

what role does the HPA axis play in stress?

Answer 41

hypothalamus: modulates pituitary gland anterior pituitary: associated with hormones, adrenocorticotropic hormone (ACTH) posterior pituitary: release oxytocin and vasopressin adrenal: cortisol (a glucocorticoid) binds to membrane-bound glucocorticoid receptors (GRs) located on CRH neurons in the PVN of the hypothalamus, this triggers endocannabinoids production which inhibits glutamatergic activation of CRH neurons which reduces CRH and the stress response

Question 42

how does chronic stress affect the BLA?

Answer 42

stress-induced structural changes in the BLA correlate with the development of anxiety-like behavior, increased plasticity in the BLA cause enhanced anxiety behavior and maladaptive behavioral changes (and PTSD)

Question 43

how does chronic stress affect the PFC?

Answer 43

stress leads to decreased dendritic length and complexity in certain populations of the PFC neurons which means the PFC cannot regulate the rest of the brain as effectively

Question 44

what effect does stress have on memory?

Answer 44

stress long before forming new memories impairs memory formation stress shortly before or after new information enhances subsequent memory performance stress before memory retrieval impairs recall of previously learned information stress effects on knowledge updating impairs integration of new information into existing knowledge structures

Question 45

what brain regions are altered in bipolar disorder?

Answer 45

smaller volumes in bipolar patients: hippocampus, thalamus, amygdala larger volumes in bipolar patients: lateral ventricles ventricular volume increases correlated with decreases in subcortical volumes

Question 46

how does lithium effect the brain?

Answer 46

neuroanatomical effects: increased grey matter volume and density in specific brain regions: amygdala (involved in emotion processing) hippocampus (important for memory and emotion regulation) prefrontal cortex (critical for executive functions and mood regulation) cellular and molecular mechanisms: affects second messenger systems, promotes cellular viability and neuroprotection, affects neurotransmitter systems

Question 47

what is the mechanism of action of lithium?

Answer 47

dopamine and glutamate are elevated during mania is bipolar patients, lithium inhibits excitatory neurotransmission by decreasing pre-synaptic dopamine activity and modulating post-synaptic G-proteins, it also modulates glutamatergic neurotransmission by initially stimulating and then chronically downregulating the NMDA receptor, and inhibiting the myo-inositol (mI) second messenger system, which is involved in maintaining signaling efficiency, additonally lithium promotes inhibitory neurotransmission by facilitating the release of GABA and upregulating the GABA-B receptor

Question 48

what is the mechanism of action of valproic acid?

Answer 48

VPA improves manic-like symptoms but not depressive symptoms by: acetylation promotes a more open chromatin structure and increased transcriptional activity, deacetylation leads to a more condensed chromatin structure and gene repression, HDAC inhibitors like valproic acid (VPA) shift the balance toward increased acetylation, this results in a more relaxed chromatin conformation and upregulation of gene transcription

Question 49

how can you assess the validity of an animal model for mental disorders?

Answer 49

face validity: how well a model mimics symptoms of a disorder construct validity: assesses whether the underlying mechanisms in the animal model are similar to those thought to be involved in the human disorder predictive validity: the ability of the model to mimic treatments for the disorder

Question 50

what are some experiments with optogenetics done on the amygdala?

Answer 50

used optogenetics to selectively activate or inhibit BLA terminals in the CEA in mice, found that activating BLA terminals in CEA reduced anxiety behaviors and inhibiting the BLA terminals in the CEA increased anxiety behaviors

Question 51

what role does the bed nucleus of the stria terminalis (BNST) play in anxiety disorders?

Answer 51

BNST is considered part of the extended amygdala, BNST lesions reduced anxiety like behaviors, spider phobics showed increased activation in the BNST during spider vs mushroom anticipation compared to controls, when ovBNST activity is inhibited, it leads to reduced anxiety in rodents, adBNST to lateral hypothalamus (LH): Stimulating this pathway decreases anxiety-related behaviors

Question 52

how do benzodiazepines effect GABA transmission?

Answer 52

GABA A: ionotropic (ligand-gated ion channels), primary target for benzodiazepines GABA B: metabotropic (G-protein coupled receptors), pentameric GABA binding its receptor allows Cl- to enter the neuron which hyperpolarizes the cells and reduces AP, benzodiazapines act as positive allosteric modulators of GABA A receptors (enhance the effect of GABA at the receptor, increasing frequency of Cl- channels opening which inhibits neurotransmission), anxiolytics effects mediated by alpha 2 subunit and sedative effects are mediated by alpha 1 GABA A receptors overall BDZs cause more frequent openings of the GABAA channel, hyperpolarization, and increased receptor affinity for GABA and act mostly in the amygdala

Question 53

how do barbiturates effect GABA transmission?

Answer 53

barbs enhance GABA A receptor function but they bind to a different site, at low doses, they increase the duration of chloride channel opening, at higher doses they can directly activate the channel in the absence of GABA

Question 54

what is the incentive-sensitization theory of addiction?

Answer 54

liking (hedonic impact): drug gives a pleasurable experience wanting (incentive salience): motivational aspect of a reward across time the liking decreases and wanting increases, wanting persists long after drug use stops, making people vulnerable to relapse especially when exposed to drug-related cues or contexts

Question 55

what is the homeostatic theory of addiciton?

Answer 55

views addiction as a disorder of disrupted homeostasis in brain reward and stress symptoms, as addiction cycle goes on mood drops further and further below the homeostatic set point following drug use, this means individuals will need to use drug to even reach their normal homeostatic set point, this leads to a allosteric negative emotion state/down regulation of the reward system (less dopamine release), transition from positive reinforcement (drug use for pleasure) to negative reinforcement (drug use to alleviate negative withdrawal states)

Question 56

how were the pleasure centers in the brain discovered?

Answer 56

intracranial self-stimulation (ICSS) of the medial forebrain bundle (which contain ascending dopamine fibers from the VTA to the nucleus accumbens) are part of the reward and motivation pathway with the lateral hypothalamus, VTA and prefrontal cortex are also effective sites, found that animals will work hard to get ICSS suggesting its rewarding properties

Question 57

what are some characteristics of the substantia nigra (SN) dopaminergic system?

Answer 57

SN plays crucial role in movement control and contains dopamine neurons that project to the striatum (nigrostriatal pathway), this pathway is critical for motor learning and execution

Question 58

what are some characteristics of the ventral tegmental area (VTA) dopaminergic system?

Answer 58

VTA plays a key role in the mesocorticolimbic dopamine system, it’s involved in both “wanting (incentive salience) and “liking” (hedonic impact) aspects of reward, the VTA is crucial for positive reinforcement and reward prediction error

Question 59

what does the nucleus accumbens (NA) do and what type of dopamine receptors reside there?

Answer 59

the NA is a key brain region involved in regulating reward, motivation, and pleasure-related behaviors with dopamine release being intensity dependent D1 receptor-expressing medium spiny neurons promote reward-related and drug-seeking behaviors D2 receptor-expressing MSNs tend to inhibit these behaviors

Question 60

what are the pain areas of the brain?

Answer 60

sensory processing area: primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2) emotional/limbic areas: anterior cingulate cortex (ACC) and insula (higher ACC activation correlates with perception of more unpleasantness and ACC to NA is necessary for social transfer of pain) cognitive/associative areas: prefrontal cortex (PFC) subcortical areas: thalamus and cerebellum

Question 61

how does attention and emotion alter pain?

Answer 61

attention affects the sensory-discriminative aspects (how intense it feels), emotions affects emotional-affective aspects (how unpleasant it feels)

Question 62

what are the emotion and attention circuits of pain modulation?

Answer 62

the emotional component of pain primarily works through ACC to PFC and (PAG) when our emotional state affects how unpleasant pain feels, this circuit becomes active, when distracted from pain activation decreased in the rostral ACC, which processes emotional pain responses the attention-related circuit involves the superior parietal lobe (SPL) to both the primary somatosensory cortex (S1) and the insula, when distracted from pain activation increased in the dorsal ACC

Question 63

how does the placebo effect reduce pain?

Answer 63

when someone perceives a placebo but believes it will reduce their pain, their brain activates a specific pain-control network involving the ACC, PFC, and PAG, when naloxone was used as an opioid antagonist the placebo effect disappeared suggesting that the opioid system plays a role in placebo pain relief