ADSC/POUL 3550 Quiz 3

Understanding the Behavior

- Intelligent use of response measures depends upon a solid understanding the natural variation and biological significance of the response - For example, vocal responses to pain in piglets include two classes of calls that are divided by the frequency or "pitch" of the call.

Prolactin

- Is associated with nurturing feelings and promotes the bonding associated with parenting behavior - Increased level of prolactin have been seen in chickens during social bonding

Can you light my pre-frontal corex?

- MRI scan of people madly in love when asked to think about their beloved. Activity can be seen in ventral tegmental area (left arrow), associated with euphoria and addiction. Activity was also observed in pre-frontal cortex (right arrow), associated with thinking and reward

Validating Behavioral Measures (Experiment Results)

- The authors concluded that quantifying post-surgery behavior was an effective pain scoring method following abdominal surgery in rats o They were also able to say that 1 mg/kg meloxicam significantly reduces laparotomy-induced pain o Since only a short observation period was required, this method can be used practically to assess severity of pain and to test potency of additional clinical analgesics

Why Study Pain?

- The study of pain provides a good starting point for the study of animal feelings and emotions o Pain is unpleasant o Involved neural structures common to most animals o Pain is perceived by sensory neurons and can result in simple refluxes and in some cases can involve higher order cognitive processing - Emotional states such as pain are subjective and one can only be certain of one's own experiences

Feedback Action and Timing

- The various feedback loops that regulate the HPA differ in action and timing o Feedback can be fast, intermediate, or genomic o Fast = termination of ACTH release as circulating glucocorticoids rise o Genomic = changes in transcription of HPA-related genes either up or down to alter the capacity of the HPA axis and thus its sensitivity to stress - Feedback from the hippocampus lowers the activity of the HPA by downregulating synthesis and release of CRH and AVP o Feedback from the hippocampus can also help terminate the stress response o Termination of the stress response slows in aging animals.

Treat Immediate pain

Nerve block (eg., lidocaine)

Treat Longer-term pain

NSAID (eg., ketoprofen)

Autonomic Response

Smooth muscles and cardiac

Head Shakes after Dehorning

What was the less painful option? - Caustic Paste (want to be no head shakes during the dehorning)

Regulation of HPA: Feedback

- Feedback regulation of the HPA occurs mainly via glucocorticoids on pituitary, hypothalamus, and suprahypothalamic sites o Most feedback is regulated by glucocorticoid binding to two classes of receptors o Glucocorticoid receptors (GR) o Mineralocorticoid receptors (MR)

What is pain?

"Pain in humans and other animals can be defined as the unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage."

Functional Anatomy of Brain

* See Chart *

Cognition and Welfare

- "The mental action or process of acquiring knowledge and understanding through thought, experience, and the senses" - "All forms of knowing and awareness, such as perceiving, conceiving, remembering, reasoning, judging, imagining, and problem solving" - Cognitive ability in animals is a direct result of brain function and has potential implications for animal welfare - o First, many domestic animals demonstrate substantial cognitive ability. Humans tend to regard animals more highly when they are more similar to us in cognitive skills. (Dogs and cats vs. chickens)

Neurobiology of Stress

- 5 brain regions - Brainstem pathways (many cholinergic) transmit visceral information - Midbrain and pons relay somatic and special sensory information - The forebrain relays information from components of the limbic system that mediate cognition and emotion - Circumventricular organs in the brain convey information about blood borne chemosensory signals - Other regions of the hypothalamus may provide information about motivational states or serve to integrate other inputs

Tracking up

- A cow is tracking up when the hind claw falls on or in front of the foreclaw print from the hoof on the same side of the body. Deviations are shortened strides in which the hind claws do not approach the foreclaw prints; this distance becomes greater with increasing severity of the defect.

Behavioral Measures

- Behavioral responses to pain can be unique to each species - Can provide clue about the presence, location, and severity of pain - Behavioral changes that must be considered in animals are o Aggression o Vocalizations o Self-mutilation o Social Interaction o Sleep Alteration o Restlessness o Lethargy

Validating Behavioral Measures

- A study by Roughan and Flecknell (2003) evaluated 7 behavioral activities to determine if they could be useful for evaluating pain in rats o For these behaviors to be useful in evaluating pain in laboratory rats they must be shown to occur after different types of surgery, and frequently enough to allow rapid scoring of animals. o Here, the authors looked at does-related analgesic induced reductions in the occurrence of their chosen behavioral activities following midline laparotomy in rats. - Experimental set up - 57 male Fischer rats were divided into groups to receive either saline (0.2 ml/100g s.c.) or meloxicam (0.5, 1 or 2 mg/kg s.c.) 1h before surgery - Behavior data were collected for 10 min following 25 min of recovery from isoflurane anesthesia - The cumulative frequencies of back arching, fall/stagger, writhe and poor gait were used to compute a composite behavior score

Testing Cognitive Abilities

- A stumbling block in examining cognitive ability or sentience in animals is designing tests that accurately test their abilities o The tests must be appropriate for and usable by the species of interest o Many early tests were not sufficiently challenging or did not use appropriate motivation, which made researchers think animals did not have advanced cognitive skills

Gait Assessment

- As an example of pain scoring systems, let's consider systems we use to detect a painful ailment common in dairy cattle - lameness o Gait defects in cattle are normally scored using a Numerical Rating Score (NRS) based on the presence of a number of gait defects explained on the following slides o However, each of the defects could also be scored using a Visual Analogue Scale (VAS) o Some of these gait features can also be scored objectively using instruments like pressure or force plates

Norepinephrine/ Nonadrenaline

- Associated with attentiveness, sleeping, and dreaming in humans - Decreases in depressed human patients

Phenylethlylamine

- Associated with feelings of attraction, exhilaration, apprehension, and elation - Similar to substance found in chocolate, which may account for chocolate cravings experienced by some people

Oxytocin

- Associated with feelings of joy, happiness, and bonding - In rats, elevated levels of oxytocin are seen in situations related to bonding and attachment, social, maternal, sexual behavior, and stress relief

Why Brain?

- Brain regulates nearly all coping mechanisms - Base for all senses including pain - Also controls the ability of animals to learn and adapt and to experience emotions

Behavioral Measures (Cats vs. Dogs)

- Cats o Hide or evade interaction o Excessive licking o Severe pain can cause rigid posture - Dogs—exaggerated responses o Aggression—acute pain o Depression, submission o Licking of the affected zone o Lethargy o Severe Pain § Vocalizations § Increased production of tears § Wandering § "Prayer Position"

Production Measures

- Change in feed intake, water intake - However, productivity measures do not reflect what is happening to the animal now, but rather what was happening over the interval between observations (typically hours for food and water consumption and days for changes in body weight)

Neurobiology of Stress (Chronic Stress)

- Chronic stress can affect brain function in many ways o Impaired learning and memory o Damage to hippocampal neurons and remodeling of hippocampal dendrites o Suppression of neurogenesis o Changes in neurotransmitter distribution and/or levels o Disorganization of brain function - Psychological stressors are among the most potent stimuli in eliciting changes in HPA axis function

Cognitive Ability Test (Corvid)

- Cognitive tests have been used to examine spatial ability in corvids (members of the crow family including crows and jays) o Many corvids cache seeds for consumption later o In the wild, these birds have been observed to remember the location of hundreds of seeds that they have hidden o However, in lab settings corvids seemed to be unable to remember the location of very few seeds o Researchers concluded that birds in the lab were not motivated to find the seeds accurately in the lab setting. They may not have been hungry enough, they may not have used sufficient extra energy when wrong to force them to be more accurate, or they may have enjoyed exploring the novel environment for stimulation

Interspecies Communication

- Communication between species is possible for most domestic animals Examples: Dogs are skilled at reading human communication signals after centuries of evolution

Neurobiological Measures and Animal Welfare

- Constant interaction between the body and brain of an animal o Sensory information from body to brain o Motor information from brain is relayed back to the body and results in action o Resulting action can be somatic (reflexive physical movement), autonomic response (smooth muscles and cardiac)

Castrating at Younger Ages

- Contrary to common belief, call rate increases during castration regardless of piglet age.

Pain Assessment

- Now we know the reasons/importance of studying pain, let's consider about assessment of pain - 3 critical aspects of pain assessment o Validating measures o Objective vs. subjective assessments o Understanding the behavior

Effects of Stress on Emotions

- Emotions are FEELINGS o Psychic or physical reaction (anger, fear) subjectively experienced as strong feeling and physiologically involving changes that prepare the body for immediate vigorous action - Detailed research in humans - Most research has taken an approach that tries to describe stress on a continuum between the pathogenic or salutogenic o Did the stress result in dysfunction (pathogenic)? o Did the stress result in psychological insight, strength or growth (salutogenic)?

Emotions and Neurobiology

- Emotions are affective or subjective states o Neurological responses to many emotions have been detected o These responses are often associated with specific brain regions or pathways - Happiness o Hypothetically, happiness could range from serenity through ecstasy

Refinement

- Encompasses methods and techniques that alleviate or minimize potential pain and distress during the experiment - Refinement also works to enhance animal well-being during experiments

Replacement

- Encompasses methods that permit results to be obtained without conducting experiments or other scientific procedures on animals - Consideration should be given to alternative methods that do not involve use of animals - Computer simulations, modeling, and in vitro work with cell cultures are alternative means to neurobiological research

Pain Mitigation

- Even when people acknowledge the potential for animals to experience pain, appropriate treatment does not always follow - For example, a study examining the attitudes of French veterinariansfound that 96% of respondents were ''moderately or extremelyconcerned about recognition and alleviation of animal pain''(Hugonnard et al., 2004) o However, for cats and dogs, analgesic use by respondents ranged from a highof 84% following orthopedic surgery to a low of 17% following castration o The top two reasons provided for a lack of treatment were ''difficulties in recognizing pain'' and ''lack of knowledge about appropriate therapy'',highlighting the need for further research and training in this area

Fear

- Fear is defined as a motivational state aroused by specific stimuli that give rise to defensive behavior or escape - Hypothetically, fear can range from apprehension through terror - Animals may learn to fear situations in which they have previously been exposed to pain or stress, and subsequently show avoidance behavior when they reencounter that situation - The fear response is well-orchestrated, uses very simple neural pathways, and leads to predictable outcomes o What is that response called? - In humans and other animals, the amygdala is the primary area of the brain that processes fearful stimuli

Limbic Input

- Forebrain limbic areas such as the hippocampus, prefrontal cortex, and amygdala project to the PVN via the stria terminalis o These areas mediate cognitive, emotional, and affective influences upon the HPA o The extent of activation or mediation from these multi-synaptic circuits is the topic of a great deal of research

Locations of GR and MR

- Found in most regions of the brain - High numbers of receptors are found in the frontal cortex, amygdala, PVN, and hippocampus

Happiness and Brain

- Functional magnetic resonance imaging (fMRI) reveals that certain areas of the human brain characteristically respond when a person is presented with visual stimuli that make them happy

Reduction

- Gaining inferences from data using fewer animals in the experiment o Repeated samples o Multiple samples from same individuals o Using same animals in multiple experiments

Validating Response Measures

- How do we know that the response we are measuring is telling us something about the pain felt by the animal? - Think of the following situation o X = a condition causing pain o x = without a condition causing pain o Y = with analgesic o y = no analgesic - For the most useful and valid measures of pain: - The painfulness of XY = xY = xy - The painfulness of Xy >> (XY, xY, and xy)

Sadness

- Hypothetically, sadness could range from pensiveness through grief

Reluctance to bear weight

- Ideally a cow should bear her weight evenly on all fair legs as she stands and walks. Deviations from this include a slight limp to a marked reluctance to put any weight on one or more limbs. The more strongly the animal avoids putting weight on the limb, the greater the defect.

Head bob

- Ideally the cow's head should remain steady as the animal walks. The more pronounced the vertical movement of the cow's head, the greater the severity of the defect.

Emotional Homeostasis

- Important to maintain emotional balance or homeostasis in the face of stress in order to be psychologically healthy - Emotional homeostasis does not imply that the person, or animal, must always experience neutral emotions, but that on the whole, their emotions are balanced and regulated - For people with the ability to recognize and influence their emotions, the emotional pendulum swings between pleasant and unpleasant, but is generally in the central range - For people who fail to recognize and control their emotions, the emotional pendulum swings wildly and erratically between states

β-endorphin

- In humans it has been associated with feelings of euphoria (runner's high) and analgesia, and is seen in distressful situations. - Levels of β-endorphin are elevated in monkeys during affinitive grooming and sexual behavior

Changing Attitudes to Pain

- In the late 1800's, many human patients were not provided with anesthetics even though these were widely available and inexpensive. o The rich, whites, and women were more likely to receive anesthetics, but not their social opposites o Babies that were too young to speak were also considered unable to feel pain in the same way that adults did - Currently research and society are becoming concerned with questions of pain in babies and animals and methods to alleviate such pain - Acknowledging potential painful scenario is one thing, but to study pain scientifically is difficult.

Brainstem Input

- Input from the brainstem generally stimulates HPA activity o Catecholamines such as norepinephrine and serotonin are key neurotransmitters o Some subtypes of serotonin receptors are sensitive to glucocorticoids, allowing for feedback o Galanin, substance P, and neuropeptide Y may affect HPA activity via the brainstem

Hypothalamic Input

- Inputs project to the PVN from nearly all regions of the hypothalamus (except supraoptic and mammillary nuclei) o This creates a complex picture of functional roles of the various pathways. o Projections from the arcuate nucleus, for example, release ACTH, β-endorphin, neuropeptide Y, and dopamine.

Confinement and Developmental Stress

- Many domestic animals or animals in captivity undergo stresses at potentially sensitive periods during development - Weaning of cows and pigs at young ages, removal of cats and dogs from mother/pack to human homes—too early or too late can be bad, neonatal interventions experienced by most production species: castration, dehorning, teeth clipping, ear notching, branding, etc - Social recognition and spatial learning and memory in pigs can be impaired by social isolation following early weaning - Exotic animals (e.g., cetaceans and primates) born into captivity may not experience full range of environmental stimuli needed for proper development

Physiological Measures

- Measures include responses of the sympatho-adrenal system, such as changes in heart rate due to release of norepinephrine, and responses of HPA axis, such as changes in concentrations of cortisol, ACTH, and CRH. - Useful mainly in prey species—minimal behavioral responses - Less useful for on-farm assessments - Measurements themselves require animal restraint and tissue sampling—confound the results - Physiological parameters are affected by many factors (fear, stress, etc.) o Not a reliable tool for precise assessment of pain by itself o Can be used as a basis for recognizing process related to pain o Chronic pain—less evident - Lactate level in blood—severity of tissue damage after a traumatic event (or a severe metabolic sickness)

Objective vs. Subjective

- Measures of pain can vary in their objectivity

Recognition of Conspecifics

- Most farm animals are capable of recognizing some individual conspecifics o Recognition involves generalization, concept formation, and discrimination. o Recognition of an individual means that a unique label is applied to that individual to distinguish it from others of the same species. Examples: Cattle can discriminate the faces of other cattle / Sheep can recognize the faces of conspecifics and of humans

Dopamine

- Needed to enjoy pleasurable stimuli; Increases with pleasurable sensations, copulation in males, feeding, and drinking - Associated with feeling of being energized - Low levels often associated with depression in humans

Approaches to Pain Assessment

- Pain assessment in animals has tended to use one of three approaches o Basic production measures o Physiological measures o Behavioral measures - All three approaches have merit and can be useful in different contexts

Summary (Pain)

- Pain in animals is an important societal concern and a challenging area of scientific enquiry - Validated and reliable methods of pain assessment can be developed for different applications - Using these measures, we can identify ways of treating the pain and ways modifying the procedure to cause less pain. In some cases, we can reconsider the procedure altogether

Avoiding Confounds

- Physical injuries and diseases can also cause a loss in normal functioning, regardless of whether pain is present - The XY versus Xy treatment can allow us to determine if it is loss of function or pain causing the change in response - For example, joint injuries may prevent normal movement of the joint, leading to stiffness in gait that may not be associated with pain o The use of an analgesic treatment allows us to distinguish the effect of pain from other effects of the condition o However, analgesic treatment (by itself) can have general inhibitory or excitatory effects on behavior, such as the well-known sedative effects of opiates o Thus, it is also important to examine the responses of uninjured animals with and without analgesics to determine if the analgesic causes a difference in the behavior even in the absence of pain

Stage of Development

- Pregnancy and Parturition o During pregnancy and parturition, memory deficits and changes in perception of pain have been observed - Aging o Aging can cause dysregulation of the HPA axis such as delayed recovery to basal HPA activity after stress o This may be due to decreased MR and GR binding and less mRNA for these receptors in the hippocampus

Brain Input to the HPA

- Prior to the initiation of the stress response, the PVN sums and integrates input from numerous locations in the brain to determine if a stress response (i.e., release of CRH and start of the cascade) will occur in response to a stimuli - Brain areas that send input to the PVN (and therefore provide input to the HPA cascade) can be broadly divided into five classes

Serotonin

- Proper regulation of Serotonin relieves feelings of depression and anxiety - Low levels can lead to impulsive acts, insensitivity to future consequences, aggressive behavior, risk taking, and suicidal tendencies in humans

Tail Docking Dairy Cattle

- Some dairy producers believe that tail docking will keep cows cleaner and reduce the risk of udder disease - Research provides no evidence to support this belief o Cattle with docked scores are not significantly cleaner than cows with long tails o No reason to dock tails if the aim is to keep cows cleaner to reduce mastitis

Higher Cognitive Processes

- Some species of animals have been demonstrated to display awareness of self, awareness of thoughts and emotions of others, and the ability to knowingly deceive others o Higher cognitive processes include concept formation, object permanence, spatial representation, and mental state attribution

Sadness and the Brain

- The areas of the brain that respond to sad images do not respond when the person is presented with neutral images - This indicates that the response is not due to visual processing of the images, but rather to the emotion elicited by the images

Modifying the Procedure

- Sometimes pain can be reduced by changing the procedure - Unfortunately, some popular modification intended to reduce pain actually have little effect o For example, it is commonly assumed that certain procedures, such as castration, cause less pain if performed at an early age - However, some modifications do work well to reduce the pain associated with a procedure - For example, housing systems can be modified to prevent or help recovery from painful injuries - Gait improves when animals are simply moved to pasture from free stall barns.

Stereotypies and the Brain

- Stereotypic behavior can be correlated with changes in the brain. In particular, changes in patterns of opioid receptors have been related to stereotypic behaviors o Sows with stereotypies may have different patterns of opioid receptors in frontal cortex than pigs that do not show stereotypic behavior (Zanella et al., 1996). This could be a direct consequence of GR activation o Such sows may also have different numbers of dopamine receptors and/or dopamine concentrations in the frontal cortex (Zanella et al., 1998) and in the nucleus accumbens (McBride & Hemmsings, 2001)

Stress during Development

- Stress at sensitive periods of development may permanently alter the stress response and coping ability of the animal - Prenatal Period o Prenatal stress may result in physical and behavioral alterations in the offspring, including higher circulating levels of glucocorticoids and a hyper- responsive HPA - Neonatal Period o Mild neonatal stress may result in less anxious animals with reduced responsiveness in the HPA (rats subjected to short maternal separation) o This type of stress can reverse the effects of prenatal stress

Stress and Affective States

- Stress can decrease or increase the ability to feel a particular emotion or affective state. It can also influence the threshold at which the state/emotion is experienced o Anger o Disgust o Fear o Happiness o Sadness

Stress can Alter Coping Mechanisms

- Stressful situations can alter coping systems in the brain in several ways o Impairing cognitive processes o Impairing reward systems § reducing release or re-uptake of neurotransmitters such as endogenous opioids, dopamine, or serotonin o Compromising the ability of animals to process "emotional" information § Causing learned helplessness or depression

Evidence for Analogy

- Structures and pathways used to send and receive pain are well studied in humans and animals, and much is known about mitigating pain using pharmacological agents o This makes pain suitable for study - For the argument by analogy to hold, there must be evidence that supports drawing analogies - If we were to argue by analogy that kids feel pain when they are castrated because humans would feel pain in this case, evidence could be based upon similarities in:- Behavioral response to pain o High-frequency vocalization - Neuroanatomy o Similar type of nerve endings/receptors, neuronal pathways and tracts, brain structures -Neuropharmacology and responses to analgesics o Vocal response can be reduced by using local anesthetic suggesting reduced pain

Stress Can Alter the Brain

- Temporary o Reversible memory disruption (short term memory loss) o Temporary disruption of reward systems (eg, inability to feel pleasure) o Emotional dysregulation (eg, persistent fear, increased aggression, attention deficits, or lack of impulse control) - Permanent o Long-term cognitive impairment o Established stereotypies o Anhedonia o Emotional dysregulation

Lameness in Cattle

- The Numerical Rating Score based on these behaviors relate to the pain cows experience. As shown below, the lameness scores are reduced when animals are given Ketoprofen.

Emotion and Welfare

- The brain controls emotions and feelings, and animal welfare at its most basic level is concerned with alleviation of animal suffering o There is no single pleasure center in the brain, but there are certain neurotransmitters that are released during pleasant experiences o Changes in the levels of these transmitters as animals experience certain stimuli or conditions can be measured to gauge whether the animal perceives the experience as pleasant or stressful

Practical Approaches to Treating Pain

- The challenge in developing treatments is to ensure that these are both affective and sufficiently practical that producers can adopt them.

Circumventricular Organs Input

- The circumventricular organs are areas of the brain located along the borders of the 3rd and 4th ventricles. These unique areas have an incomplete blood-brain barrier and are important sites for communicating between the brain and peripheral organs via blood-borne products and cerebrospinal fluid. o Circumventricular organs include the pineal gland, median eminence, subfornical organ, area postrema, subcommissural organ, and organum vasculosum of the lamina terminalis as well as the intermediate and neural lobes of the pituitary o Sense blood-borne signals such as concentrations of angiotensin II § The CVO relay information to the PVN, mainly to neurons involved in water balance § Stress-related neurons may also be affected

Midbrain Input

- The colliculi, periaqueductal gray, and pons contain neural pathways sensitive to sensory stimuli (audition, nociception, and vision/ audition respectively) o These regions may also affect HPA activation o Cerebral peduncles play role in body coordination

Asymmetric steps

- The cow's steps should exhibit symmetry as the legs swing forward; deviations are seen as increasing asymmetry of motion between the right and left pairs

Cognition and Emotion

- The emotional state of an individual may affect his/her interpretation of events o People in a negative emotional state see ambiguous things as negative o People in a positive emotional state see ambiguous things as positive - This is called cognitive bias o Rats, dogs and starlings are animals who have been shown to demonstrate cognitive bias

Joint flexion

- The ideal is a cow whose legs exhibit flexion at the joints rather than stiffly swinging the limbs forward. As stiffness in the joints increases, the defect becomes more severe.

Swinging in/out

- The ideal is a hind leg that swings forward with each step parallel to the median plane of the body. Deviations are the leg swing towards (abduction) or away (adduction) from the median plane of the body as the animal steps. The greater the amount of swing as the leg moves forward, the more severe the defect.

Brain Development and Welfare

- The neural organization of the brain occurs at an early age and will influence the ability of an animal to respond to or cope with difficult situations throughout life (welfare) - The social environment is a very important to help the developing brain of young animals form the necessary interconnections among brain regions o Mother and infant interactions o Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex (Kikusui et al., 2019)

Neurobiology of Stress: HPA Quick Review

- The paraventricular nucleus (PVN) of the hypothalamus releases corticotrophin releasing hormone (CRH) - CRH causes release of adrenocorticotrophic hormone (ACTH) from the corticotropes in the anterior pituitary - ACTH travels via the blood to the adrenal gland, where it activates cells in the adrenal cortex to stimulate the synthesis and release of glucocorticoids - Glucocorticoids then travel in the blood stream to exert negative feedback on the PVN and the anterior pituitary

Influences on HPA Responses

- The stage of the animal's development or physiological status may influence the response of the HPA system to stress - Neonatal Period o Rats less than 2 weeks old have a hyporesponsive HPA o This may be due to immature afferent connections to the PVN o By 4 weeks, rats have a normal stress response

Inputs to the HPA

- Together the inputs to the HPA may help integrate various stimuli. In some cases, some pathways take precedence over others (e.g., visceral over motivational) o Some pathways may only be selectively activated by certain stimuli while others may respond more generally to a wide range of stressful stimuli o Stimuli may be coded in order to weigh some stimuli more heavily than others in the decision to activate the HPA

Binding of Receptors to GC

- When there are low levels of glucocorticoids (GC), MR are preferentially bound because MR receptors have higher substrate affinity than GR o The dissociation constant (Kd) for MR = 0.5 nM while for GR Kd =5nM § (Kd refers to the concentration at which the two bound molecules will separate) o Because MR has a lower dissociation constant, MR will still be bound to GC at lower concentrations than GR - As levels of GC rise, as in stressful situations, MR receptors become saturated, and more GR receptors become bound - When GC levels remain elevated for longer periods, such as in situations of chronic stress, production of MR may be upregulated to help buffer the stress response

If the procedure is really necessary:

Group on the Left = Beaks were trimmed Group on the Right = Beaks were NOT trimmed

Neurotransmitters associated with pleasant experiences:

Oxytocin, Dopamine, Serotonin, Prolactin, β-endorphin, Phenylethlylamine, Norepinephrine/ Nonadrenaline

Somatic Response

Reflexive physical movement

What are the 3 R's regarding the use of animals in research?

Replacement, Reduction, and Refinement

Treating Distress associated with restraint

Sedative (eg., Xylazine)