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Answers to quiz and questions at end

Step 1

  1. Rote memorise this pdf: File:Behavioural Screening Prac-student self learning.pdf
  2. Fill in this table (all answers are in the pdf)
Behaviour Hexobarbital Morphine Amphetamine Picrotoxin
Ataxia X
Corneal reflex Reduced
Clonic convulsions X
Dyspnoea X
Hypertonia X
Hypotonia X X
Miosis X
Opisthotonus X
Piloerection X
Ptosis X
Respiratory depression Shallow breathing Slow breathing
Salivation X X
Sedation X X
Spasms X
Stereotypies X
Straub tail X
Wet dog shaking X

Step 2

  • Watch the videos
    • Checking out the responses of the animals when you give them the drug
    • Sequences are increasing in time from dose
  • Hexabarbitol
    • Barbiturate - used for epilepsy, not as common, used for anaesthesia, animal surgeries
    • Sequence 1: Increasing ataxia and hypotonia; shift to procumbent posture
    • Sequence 2: Anaesthetic stage 2-3, animal still has reflexes (e.g. corneal reflex), defensive reflex on pinching ear (shaking of paw and head)
    • Sequence 3 (time 3-4 minutes): anaesthetic stage 3. No defensive reflex on pinching ear. Respiration influenced by pinching. Corneal reflex present
    • Sequence 4: stage 3-4, no pinch test, no corneal reflex, respiratory depression, respiration uninfluenced
  • Morphine
    • Sequence 1 (20-30 minutes after morphine injection). Treated group shows sporadic high levels of locomotor activity with resting intervals, running along walls, no standing on hind legs, against cage walls. Generally separate from each other (breakdown of group cohesion). Slighltyly humpbacked posture, pelvis depressed, Straub tail, walking on tiptoe with short, rapid movements
    • Sequence 2 - humpacked posture, short, rapid movements
    • Sequence 3 - humpbacked posture, short, rapid movements, sporadic activity, salivation (apparent from wet fur on head)
    • Sequence 4 (2 minutes after injection of rabbit) - animal quietens and lies down
    • Sequence 5 (10-15 minutes after injection of rabbit) - respiration slow (bradypnoea) and shallow. Eye-miosis
    • Sequence 6 (20-25 minutes after injection) - ptosis, sedation (waking rabbit results in brief activation, eyes oppened normally, animal afterwards lies down again). Respiration irregular after lying down, rapidly becoming slower (bradypnoea) and shallow (inhibition of respiratory centre)
  • Amphetamine (ADHD, narcolepsy)
    • Sequence 1 (shortly after injection) - normal exploratory behaviour with adoption of erect posture. Rat explores whole cage and exhibits locomotion, standing on hind legs, preening etc
    • Sequence 2 (approx 10-15 minutes after injection) - onsetof stereotypies: rat inspects (sniffs) only at one side of the cage, remains erect and in the same place. Piloerection
    • Sequence 3 (approx 25-30 minutes after injection) - stereotypies (sign of stress): rat stands in same place, makes stereotyped head movements and always sniffs the same area of the floor. Marked piloerection (head and body)
    • Sequence 4 (approx 35 minutes after injection): stereotypies: forelegs now also involved in sterotypies - spreading of front toes. Piloerection (also clearly apparent on head)
  • Cocaine
    • Sequence 1 (15' after injection) - posture with tail extended straight out backwards. Intervals of high locomotor activity aternate with resting periods. Movement pattern normal (no short, rapid movements as in the case of morphine).
    • Sequence 2 (approx 15' after injection) - posture and movement pattern normal. Sporadic high levels of activity. Group not entirely broken down. Standing on hind legs and exploration which also includes walls. Movements sometimes jerky.
  • Picrotoxin (tool to study seizures)
    • Sequence 1 (shortly after injection) - rat behaves normally
    • Sequence 2 (5' after injection) - defecation (signs of autonomic stimulation), spasms, beginning in hind legs, later involving both fore and hind legs and developing into clonic convulsions
    • Sequence 3 (5' after injection) - wet dog shakes
    • Sequence 4 (10-15' after injection) - second attack of spasms. Clonic conbulsions, then hypertonia (apparent from slighly humpbacked posture, splayed hind legs and spreading of toes), spasms of facial musculature (twitching of ears)
    • Sequence 5 (15' after injection) - hypertonia (slighly humpbaked posture, splayed hind legs, spreading of toes), salivation, sudden seizure with clonic-tonic convulsions, opisthotonus and slow relaxation with intervenining spasms and periods of respiratory arrest, dyspnoea. During the relaxation phase the toes are spread.

Step 3

  • Basically, rats like to be inside, tucked away
  • There are open arms and closed arms to the experiment
  • If the drug has a) reduced anxiety, it heads out into the open arms more often b) increased anxiety, it stays in the close arms more often
  • Measure the amount of times it changes arms ("entries") and the total time it spends in the open arms

Quiz

Quiz for Part 1

a) Hypnotics/Sedatives

  • Q1. The barbiturates are known to produce exciting ataxia and hypotonia prior to anaesthesia. What is the other predominant behavioural characteristic observed?
    • a. Opisthotonus
    • b. Clonic convulsions
    • c. Salivation
    • d. Mydriasis
    • e. Respiratory depression (this happens after anaesthesia)
  • Q2. A subject is given an unknown drug which produces anaesthesia. Upon awakening, the patient suffers amnesia for 3 hours. The drug is likely to be a type of
    • a. Barbiturate
    • b. Opioid
    • c. Benzodiazepine
    • d. Cholinergic
    • e. Ether
  • Q3. Which of the following are the effects of benzodiazepines?
    • a. Reduction of anxiety and aggression
    • b. Anticonvulsant effect
    • c. Acts allosterically to increase of GABA for the GABAA receptor binding
    • d. Rapid eye movement (REM) sleep suppression
    • e. All of the above

b) Opioids

  • Q4. The distinguished behavioural characteristics of morphine as demonstrated in the video sequence above include
    • a. Sporadic activity
    • b. Straub tail
    • c. Hunched posture
    • d. Walking on tiptoe
    • e. All of the above
  • Q5. In addition to the decreased pain perception and sedative effects, morphine also has effects on the eye and typically produces:
    • a. Miosis
    • b. Ptosis
    • c. Mydriasis
    • d. Ptosis and Mydriasis
    • e. Ptosis and Miosis
  • Q6. Morphine produces its effects through activation of specific opioid receptors in the brain. The receptor responsible for producing most of the analgesic effects is
    • a. δ receptor
    • b. μ receptor
    • c. κ receptor
    • d. σ receptor
    • e. α receptor

c) Stimulants

  • Q7. The most prominent clinically useful effect of opioids is reducing pain. Which of the following are unwanted effects of morphine?
    • a. Euphoria and respiratory depression
    • b. Sedation and dependence
    • c. Constipation
    • d. Both a and b
    • e. a,b and c
  • Q8. The major behavioral characteristic of amphetamine as demonstrated in the video sequence above is
    • Sporadic activity
    • Piloerection (this is not behavioural)
    • Normal movement pattern
    • Stereotypies
    • None of the above
  • Q9. Amphetamine and cocaine are both drugs of dependence which are subject to abuse in the community. They have very limited clinical use. The main use of amphetamines is in the treatment of
    • a. Obesity
    • b. Attention deficit/hyperactivity disorder (ADHD) in children
    • c. Narcolepsy
    • d. Both a and c
    • e. Both b and c
  • Q10. The mechanism underlying the psychostimulant effects of cocaine is
    • a. Stimulation of catecholamine uptake
    • b. Inhibition of catecholamine uptake
    • c. Releaseofcatecholamine
    • d. Non-competitive antagonist of 5-HT receptor
    • e. None of the above
  • Q11. The convulsants form a diverse group of drugs which have varied mechanisms of action, but share a number of important behavioural characteristics, including
    • a. Clonic convulsion, salivation
    • b. Spasm, salivation
    • c. Clonic convulsion, hyperreflexia
    • d. Spasm, wet-dog shakes
    • e. Clonic convulsion, spasm
  • Q12. Picrotoxin acts as a
    • a. GABAA receptor agonist
    • b. GABAA receptor antagonist
    • c. Glycine receptor antagonist
    • d. Adenosine receptor antagonist
    • e. None of the above

Questions for Part 2

  1. Are the means of control and diazepam treated groups significantly different?
    • Yes, p <0.001
  2. How does diazepam work?
    • It is a benzodiazepine binding to GABA, enhancing the effect of GABA on GABA receptors [allosteric modulation]. It acts on the limbic system, thalamus and hypothalamus. It also inhibits processes in the cortical brain. It also has anticonvulsant effects binding to voltage-gated sodium channels.
  3. Why are we calculating open entries as a percent of the total number of entries?
    • Some rats may have low open entries normally due to different baseline activity levels.
  4. Why is important to be blind to the treatment groups when studying animal behaviour?
    • If you know the likely outcome / treatment group, you will pay too much attention / interpret behaviour based on your expectations.