Central nervous system -- Behavioural modification

What are the drug groups for behavioural modification?

1. Tricyclic depressant

2. SSRI

3. SARI

4. MAOI

5. Benzodiazepines

6. Alpah 2 antagonist

7. Azapirone

8. Drugs for anticonvulsant

   1. Calcium channel blocker

   2. Imepitoin

What is the mechanism of action of tricyclic antidepressant (TCAs)?

Block transporter of serotonin and noradrenaline → Inhibit reuptake of serotonin and noradrenaline → Increase serotonin and noradrenaline in synapse

• Serotonin is responsible for regulation of mood, appetites and arousal, fear and aggression

• Noradrenaline is responsible for learning and facilitating other neurotransmitters e.g. ACh and dopamine

Give examples of TCAs.

• Amitriptyline

• Chlomipramine

What is chlomipraine licensed for?

Licensed for separation anxiety related disorder

Which patients should be considered when administering TCAs?

Caution with heart disease

• Some TCAs block sodium and calcium channel

What is the mechanism of action of specific serotonin reuptake inhibitors (SSRI)?

Inhibit reuptake of serotonin → Increase serotonin in synapse

• Serotonin is responsible for regulating mood, appetites, arousal, fear and aggression

Give one example of specific serotonin reuptake inhibitors (SSRI).

Fluoxetine

What are the clinical uses of SSRIs?

Take 6-8weeks to reach maximum efficacy → Long term use for behaviour modification

What do we need to be aware of when using SSRIs?

• Down-regulate post-synaptic serotonin receptors if chronic use → Less effective over time

• Metabolised by the liver and excreted in urine

What is the mechanism of action of serotonin antagonist/ reuptake inhibitors (SARIs)?

Antagonise serotonin receptors → Inhibit reuptake of serotonin → Increase serotonin in synapse

• Serotonin is responsible for regulating mood, appetites, arousal, fear and aggression

Give one example of serotonin antagonist/ reuptake inhibitors (SARIs)?

Trazodone

What are the clinical uses of serotonin antagonist/ reuptake inhibitors (SARIs)?

Short term use (Anxiolytic and sedative effects)

What is the mechanism of action of monoamine oxidase inhibitors (MAOIs)?

Monoamine oxidase is an enzyme that break down neurotransmitter e.g. serotonin, dopamine and noradrenaline → Inhibition of MAO increases neurotransmitters in synapse

• Serotonin is responsible for regulation of mood, appetites and arousal, fear and aggression

• Noradrenaline is responsible for learning and facilitating other neurotransmitters e.g. ACh and dopamine

• Dopamine is responsible for rewards, pleasure, memory and regulation of emotion

Give one example of monoamine oxidase inhibitors (MAOIs).

Selegiline

What are the clinical use of monoamine oxidase inhibitors (MAOIs)?

Treat behavioural disorders of purely emotional origin in dogs e.g. depression, anxiety, fear and phobia

What are the mechanism of action of benzodiazepines for behavbious modification?

Act on hypothalamus and limbic system

• Binds to GABA-A receptors → GABA-A receptors opens → Allows Cl- flows into the neuron → Hyperpolarization → Less likely for excitable cell to fire action potential

Give examples for benzodiazepines for behaviour modification.

• Diazepam

• Alprazolam

What are the clinical use of benzodiazepines?

Short-term use or situational behavioural modification

• Especially for exposure to unavoidable fear inducing stimuli

What do we need to be aware of when using benzodiazepines?

• Metabolised in liver

  • Should NOT be used in cats since it causes fatal hepatic necrosis

  • Caution with liver disease patients

What are the mechanism of action of alpha 2 agonist?

Act on locus coeruleus

• Block alpha 2 agonist → Reduce sympathetic activity (Flight or flight response) → Calm and sedation

Give examples for alpha 2 agonist for behaviour modification.

• Dexmedetomidine

• Clonidine

What are the clinical use of alpha-2 agonist?

• Long term use with SSRI and TCAs for panic anxiety and impulsivity in dogs

• Alleviation of acute anxiety and fear associated noise in dogs

What are the mechanism of action of azapirones?

Partial serotonin agonist

Give one example for azapirones.

Busipirones

What are the clinical use of azapirones?

Stress and anxiety for cats

Which anticonvulsant drugs have anxiolytic effects?

1. Calcium channel blockers e.g. Gabapentin

2. Imepitoin

What are the mechanical action of Gabapentin?

Gabapentin binds to presynaptic Ca2+ channels → Limit Ca2+ entry into neuron  → As calcium is needed to release neurotransmitter → Release of glutamate in amygdala is reduced → Reduce anxiety

What are the mechanical action of imepitoin?

Partial agonist of GABA receptor

• Binds to GABA receptor, GABA A receptor (A ligand-gated Cl- channel)  opens → Cl- enters the neuron → Hyperpolarization → Makes the neuron less likely to fire an action potential

What are the clinical uses of imepitoin in terms of behaviour modification?

Reduction of fear and anxiety associated with noise phobias