Exam 3: SUD, Pain, and Social Interaction

Question 1

how is diagnostic criteria score used to diagnose substance use disorders?

Answer 1

score out of 11:
2-3: mild dependence
4-5: moderate dependence
6 or more: severe dependence

Question 2

what is the incentive-sensitization theory of addiction?

Answer 2

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 3

what is the homeostatic theory of addiciton?

Answer 3

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)

Question 4

positive vs negative reinforcement?

Answer 4

positive: process by which the presentation of a stimulus increases the probability of a response
negative: process by which the removal of an aversive stimulus or negative emotional state increases the probability of a response

Question 5

what is a reward?

Answer 5

an event that produces a pleasant affective experience, a reward is often defined as any event that, when made contingent upon a behavior, increases the likelihood or frequency of that behavior occurring in the future

Question 6

how were the pleasure centers in the brain discovered?

Answer 6

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 7

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

Answer 7

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 8

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

Answer 8

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 9

what is reward prediction errror (RPE)?

Answer 9

refers to the difference between the expected reward and the actual reward received in a given situation, the RPE is largely encoded by DA neurons in the VTA, positive prediction error is when an unexpected reward occurs (increase in DA activity), negative prediction error is when an expected reward does not occur (dip in DA activity)

Question 10

how does the VTA encode for the RPE?

Answer 10

as learning progresses, the dopamine response shifts from the time of reward delivery to the time of the predictive cue, this mechanism is crucial for reinforcement learning, allowing animals and humans to refine their predictions about future rewards and adjust their behavior
accordingly, after learning neuronal activation in VTA spikes when hearing the cue but does not increase any more from getting the reward, when the reward is not given following the cue activation of the VTA decreases

Question 11

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

Answer 11

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 12

in general what role does dopamine play in addiction?

Answer 12

most addictive substances ultimately increase dopamine transmission in the mesocorticolimbic pathway,
particularly enhancing dopamine release in the NA

Question 13

what role does glutamate play in substance use disorders?

Answer 13

chronic drug use disrupts glutamate homeostasis in the NA, this disruption impairs communication between PFC to NA

Question 14

what are some non contingent models of drug use in rodents?

Answer 14

non-contingent means the experimenter administers the drug, includes behavioral sensitization, CPP, and the runway model

Question 15

what is behavioral sensitization?

Answer 15

provides insight into neural adaptations in addiction, shows how repeated drug exposure leads to an enhanced behavioral response over time, the incentive-sensitization theory proposes that repeated drug use can lead to progressive enhancement in the motivational wanting effects of drugs and cues, craving is measured through measuring the sensitization in response to a second dose of drug, rats undergo a initiation phase that represents the immediate neural events that induce sensitization mainly in the VTA, the expression phase reflects long-term consequences and enduring adaptations mostly in the NA

Question 16

what did the two injection protocol of behavioral sensitization study find?

Answer 16

even a single exposure to cocaine creates enduring changes in behavioral responses, sensitized response persists long-term (for at least 3 months) even without additional drug exposure

Question 17

what did the cross sensitization protocol of behavioral sensitization study find?

Answer 17

cross sensitization is when pretreatment with one drug leads to an enhanced behavioral response to a different drug which indicates shared neural mechanisms between different drugs, within drug classes cross-sensitization between
psychostimulants (cocaine and amphetamine) had a strong two-way effect (either drug can sensitize response to the other), between different drug classes morphine pretreatment sensitizes response to
both morphine AND psychostimulants while amphetamine pretreatment sensitizes to psychostimulants but NOT to morphine

Question 18

what are some cons in the behavioral sensitization model?

Answer 18

has limited face validity, demonstrating similar phenomena in humans is challenging, in rodents just a few drug administrations can induce robust sensitization while human addiction development typically requires prolonged drug use over extended periods before problematic use patterns emerge, behavioral sensitization may better model the early neuroadaptations that occur during initial drug exposures, rather than the complete
transition to addiction

Question 19

how is conditioned place preference (CPP) used to study SUD?

Answer 19

CPP has also proven valuable for studying relapse-like behavior, researchers first extinguish the initial place preference by repeatedly exposing animals to the drug-paired environment without drug, then, they can trigger reinstatement of the
preference through either a small dose of drug or various stressors, more time in the drug-paired environment, this indicates the drug has rewarding properties, if animals avoid the drug-paired environment (called Conditioned Place Aversion), this suggests aversive effects

Question 20

what are some contingent models of substance use disorder?

Answer 20

contingent involves operant learning where the animal performs an action to get an infusion of a drug, self-administration models are used, to better model the transition to addiction (as opposed to causal use as in 1-3 hour SA sessions) seen in humans, researchers developed the long-access (LgA) paradigm, where animals can self-administer drugs for extended periods of 6-12 hours

Question 21

what is pain?

Answer 21

pain is a complex experience with both sensory and emotional components that can occur even without direct tissue damage, influenced by context, thoughts, and emotional state

Question 22

how does the mind alter perception of pain?

Answer 22

a negative expectation can completely reverse the analgesic effects of pain killers (opioid agonists), the expectation of pain releif is an important component of placebo analgesia, a state emotional state can increase pain while a positive state lowers pain

Question 23

what are the three main components of pain?

Answer 23

emotion, cognition, and pain can all influence each other, when someone is feeling anxious or depressed their pain often feels more intense, attention, memory, and decision-making all play a critical role too, distraction or mindfulness can help reduce pain intensity, when participants had painful heat applied to the leg while either experiencing a good odor or a bad odor (bad odor led to negative emotional state and therefore worse pain and vice versa)

Question 24

what are the pain areas of the brain?

Answer 24

1. sensory processing area: primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2)
2. emotional/limbic areas: anterior cingulate cortex (ACC) and insula
3. cognitive/associative areas: prefrontal cortex (PFC)
4. subcortical areas: thalamus and cerebellum

Question 25

what do studies on the emotional processing (ACC and Insula) show?

Answer 25

patients with ACC/insula damage show altered emotinal responses to pain, imaging studies show these regions activate during emotinal aspects of pain, and stimulation studies show direct relationship between ACC/insula activation and emotional/motivational

Question 26

how is pain processed in the brain?

Answer 26

participants were put in a hypnotic state and given specific suggestions to change how unpleasant they found pain, the ACC showed increased activity when pain was perceived as unpleasant and decreased activity when pain was perceived as less unpleasant, this suggests that while pain is one experience, the brain processes its sensory aspects (like location and intensity) separately from its emotional aspects (how unpleasant or disturbing it feels), ACC is specific for the emotional processing of pain

Question 27

how does social connection alter pain?

Answer 27

pain response is stronger in the dACC and anterior insula when observing a loved one in pain compared to a stranger, this suggests that our social bonds influence how we process others’ pain at a neural level, in mouse models they placed a mouse in pain near another mouse for 1 hour, the transferred pain lasted 4 hours, this demonstrates that the ACC to NA pathway is necessary for the social transfer of pain, preventing its activity stops one mouse from catching another’s pain state

Question 28

how does attention and emotion alter pain?

Answer 28

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

Question 29

what are the emotion and attention circuits of pain modulation?

Answer 29

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
the attention-related circuit involves the superior parietal lobe (SPL) to both the primary somatosensory cortex (S1) and the insula, the separation of these circuits helps explain why attention and emotion can independently influence different aspects of the pain experience (attention affecting pain intensity and emotion affecting pain unpleasantness)

Question 30

how does distraction alter pain?

Answer 30

when distracted by a cognitively demanding task there is a decrease in activity in the insula and thalamus which leads to reduced pain intensity, this increase the dACC which helps regulate attention, but decreased in the rACC which processes emotional pain responses, the OFC also shows increased activity which assists in cognitive control over pain

Question 31

how does chronic pain alter the brain?

Answer 31

patients with chronic pain showed thinning of the cortex in several key regions that control pain processing and regulation, these changes are particularly significant because they occur in regions responsible for both cognitive control and emotional processing, ACC, PFC and insula showed structural changes (decreased gray matter) and chemical changes (reduced opioid receptor binding)

Question 32

how does the placebo effect reduce pain?

Answer 32

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, positive expectations and emotions use similar mechanisms to engage the brains neural pain relief pathways, when naloxone was used as an opioid agonist the placebo effect disappeared suggesting that the opioid system plays a role in placebo pain relief, and that pain and pleasure share overlapping experiences in the brain suggesting that pain can be associated with reward under certain conditions

Question 33

how can pain be a positive factor?

Answer 33

pain and pleasure work to elicit motivation and avoidance behaviors, pain encompass the hedonic (suffering) and motivational (avoidance) aspects of a painful experience, our internal homeostatic balance is constantly optimized through the feelings of pain and pleasure, we have to endure pain to get reward which suggests that pain and pleasure are integrated in the brain (called the motivation-decision model of pain)

Question 34

what is the motivation-decision model of pain?

Answer 34

acute pain is amplified when it becomes the most critical factor, outweighing other motivations, conversely pain is suppressed when a more pressing motivation takes priority such as hunger or the pursuit of a greater reward, however, the motivation to win or achieve a personal record takes precedence over the discomfort

Question 35

what role does dopamine play in the perception of pain and pleasure?

Answer 35

dopamine plays a key role in processing both pain and pleasure, particularly in the context of seeking pain relief, chronic pain leads to a reduction in dopamine release in the NA, while pain relief is associated with increased dopamine levels in the NA shell

Question 36

how can pain be assessed in animals?

Answer 36

traditional algesiometry tests such as tail-flick, hot plate, and von frey tests
facial expressions like the mouse and rat grimace scales (MGS/RGS)
behavioral and physiological observations can also be used, in general all methods measure the withdrawal responses to noxious stimulus and the method used to induce pain should closely mirror the underlying mechanisms of actual conditions in humans

Question 37

face vs construct vs predictive validity

Answer 37

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

Question 38

how do reflexive pain tests work?

Answer 38

they evaluate behavioral responses that are evoked by applying specific stimuli to the animal, types are thermal, mechanical, and electrical stimuli tests, reflexive tests allow researchers to measure specific and quantifiable responses to controlled stimuli

Question 39

what is the von frey test?

Answer 39

a key reflexive behavioral measure of mechanical sensitivity that has become a standard method for assessing mechanical allodynia (experiencing pain to normally not painful stimuli) and hyperalgesia (heightened pain in response to normally painful stimuli) in rodents, place animals in elevated cage, poke rodents hind paw with monofilaments of different diameters, paw withdrawal, paw licking, paw shaking, and immediate behavioral response after filament removal are all positive pain responses

Question 40

what is the “up-down” method of the von frey test?

Answer 40

developed by Dixon and refined by Chaplan, approach estimates the 50% withdrawal threshold by starting with a mid-range filament force and adjusting based on the animals response, when the animal doesn’t respond the next higher force is used and when it does respond the next lower force is used, this continues until sufficient data points are collected to calculate the threshold, electronic systems can also be used to provide precise measurements of the exact force that triggers a response

Question 41

what is the tail-flick test?

Answer 41

thermal pain assessment that measures the reflexive behaviors in response to acute thermal nociception by applying heat to the tail of rodents and recording the latency until the animal withdrawals its tail, radiant heat method uses a focused beam of light while the how water immersion tests uses a temperature controlled bath

Question 42

what is the hot plate test?

Answer 42

hindpaw is placed on a hot plate until the animal withdrawals the foot or starts licking, secondary responses can include jumping, temperature ramped thermal assessment is a modification of the hot plate test where the temperature of the hot plate is slowly raised until you get a response, some problems include the fact that behaviors may vary in their sensitivity to different analgesics (opioids tend to reduce paw licking to reduce paw licking, but this may not be altered by non-opidoid analgesics), rodents also learn to anticipate heat which can cause them to move to edge to avoid heat or have decreased reaction time in anticipation of the heat

Question 43

what is the cold-plate test?

Answer 43

allows researchers to measure various responses by placing animals on a chilled surface, the duration and frequency of nociceptive behaviors and changes in posture or stance are measured

Question 44

how is non-stimulus evoked nociception measured?

Answer 44

spontaneous pain in animals can be measured with grimace scales, graded on a scale with 0 being normal and 1 being moderately, and 2 being severely changed features (fully or partially closed eyes and bulging in cheeks/nose are signs of pain), paper aimed to categorize emotions in mice by observing facial movements and linking these to specific brain regions involved in emotions

Question 45

how do rodents vocalize pain?

Answer 45

rodents emit USVs at high frequencies (around 22 kHz) which are associated with negative emotional states like fear, stress or pain, USV analysis involves recording and quantifying these vocalizations by duration, frequency, and intensity, increased USVs in the 22kHz range suggest heightened distress representing an affective pain response rather than a reflex

Question 46

which rodent models are used to study social behavior?

Answer 46

rats are better to study social behavior since they have greater reward from social behavior and are less aggressive, however, mice are used to study neurodevelopmental disorders (NDDs) affecting social behavior since they have a well-developed genetic toolbox, which allows researchers to create genetic alterations that mirror human conditions

Question 47

what are some key characteristics of social behavior?

Answer 47

they involved intricate behavioral communication through multiple sensory modalities, relies on specific social cues, requires dynamic processing and integration of information, modulated by internal states shaped by previous social experiences, interaction begins with visual recognition, then chemosensory investigation and then ultrasonic vocalizations, sex specific cues can trigger various behavioral responses

Question 48

how does oxytocin regulate social behavior?

Answer 48

play a fundamental role in orchestrating social behavior through modulating sensory detection and evaluation, facilitating approach behaviors, reinforcing rewarding aspects of social interactions, and increasing signal-to-noise ratio in sensory neurons

Question 49

how is social interaction in humans different?

Answer 49

social brain processes multiple types of information simultaneously, including direct sensory inputs and internal representations of social experiences, face to face interaction could serve as an effective model
system for future brain imaging studies of social interaction, especially when combined with
eye tracking

Question 50

what do fMRIs find was activated during social interaction?

Answer 50

subjects were shown clips of social interactions, they found that regions in the default network (medial prefrontal and medial parietal cortex) were more active, this shows that social processing is an important default function of the brain

Question 51

what brain regions are activated during cooperation?

Answer 51

patients underwent the prisoners dilemma, found that the reward-processing brain regions like the NA, caudate nucleus, ventromedial/orbitofrontal cortex, and the anterior cingulate cortex were consistently activated, found that the striatal and anterior cingulate cortex activations were only active during human interactions and not with a computer

Question 52

what role does oxytocin play in cooperation?

Answer 52

participants got either vasopressin or oxytocin before the prisoners dilemma, oxytocin increased activity in the caudate and putamen
(reward centers) and frontal lobe in men, enhancing the reward response to cooperation, in women, OT decreased activation in these areas, reducing the reward of cooperation

Question 53

how does rejection affect the brain?

Answer 53

a study told some participants they could not play after a certain point in the game, found that the dorsal ACC was more active during exclusion, ACC activation was correlated with self-reported distress, higher ACC activity = more distress, higher RVPFC activity = less distress, RVPFC appeared to regulate distress by modulating ACC activity, social pain activates similar circuits as physical pain

Question 54

what does dorsal and ventral ACC encode for?

Answer 54

dACC is more active in response to expectancy violations, supporting its role in cognitive conflict processing while vACC reacted specifically to social feedback, showing greater sensitivity to acceptance
over rejection

Question 55

what does lack of social play lead to?

Answer 55

social play leads to pleasure, with its disruption being a key indicator of various neurodevelopmental disorders, alterations in social play may be caused by autism spectrum disorder, disruptive behavior disorders, ADHD, and early-onset schizophrenia

Question 56

what systems are involved in social play?

Answer 56

opioids are in charge of the rewarding properties of social play while dopamine is in charge of the motivational aspects of play behavior

Question 57

how does the opioid system alter social play?

Answer 57

the mu-opioid receptor plays the more prominent role with the NA identified as an important site of action, mu-opioid receptors are the primary mediators of opioid effects on play, NA and medial preoptic area are key brain regions, paper found that intra-NA morphine (morphine is an opioid agonist) increased play behavior but blocking NA opioid receptors prevented systemic morphine’s play enhancing behavior

Question 58

how does the dopamine system alter social play?

Answer 58

too much or too little DA can disrupt proper play behavior, DA influences the motivation for play behavior, there is a clear dissociation between motivational effects and play expression, drugs that increase DA like methylphenidate and cocaine increases motivation to engage in play, while reducing play expression when the opportunity arises, VTA DA neuron activity directly predicted and affected the likelihood of future social encounters

Question 59

how can we study social play?

Answer 59

to study the neurobiological underpinnings of social reward in rodents the CPP is used with another rat on one side and nothing on the other side, four 15 minute episodes of social interaction produced robust place preferences, even limited tactile interaction through steel bars could still elicit CPP, when touch was completely prevented by a glass screen the rats developed a conditioned place aversion, suggesting a contact needs to be made to make the social play rewarding

Question 60

is drug use or social interaction more rewarding?

Answer 60

in CPP rats had an equal preference for a drug associated and friend associated compartments

Question 61

how does isolation alter social play?

Answer 61

social isolation enhances the motivation to seek social play, rats isolated for 24 hours before testing exhibited higher responding for social play than those isolated for only 2 hours

Question 62

how does oxytocin alter social play?

Answer 62

oxytocin (OXT) plays a critical role in social behaviors and may have therapeutic utility for the treatment of social behavior deficits, when PVN OXT neurons are activated it promotes social behaviors, inhibiting OXT projections from the PVN to the VTA reduces social interactions and preference for social contexts, stimulating PVN OXT neurons’ projections in the VTA specifically during social contexts increases the time spent interacting socially

Question 63

what are the impacts of social integration on SUD?

Answer 63

individuals with fewer social ties are more likely to engage in health-damaging behaviors like SUD, even individuals who begin drug use while socially integrated may experience increasing social exclusion as their drug use progresses, when drug use becomes compulsive it impairs social functioning which leads to social isolation, which in turn can further reinforce drug use