41. behavior modifiers

when using drugs that enhance serotonin transmission, how long does it take to see therapeutic effects?

weeks (can take 4 weeks or longer) — downregulation of post-synaptic receptors

general adverse effects of enhanced serotonin transmission

• GI upset

• sedation

• excess serotonin (serotonin syndrome)

  • interactions with MAOIs, TCAs, SSRIs, opioids

  • increased heart rate

  • increased respiratory rate

  • agitation or tremors

example of a monoamine oxidase inhibitor

selegiline/l-deprenyl

selegiline (l-deprenyl) mechanism of action

inhibits monoamine oxidase, the enzyme responsible for monoamine neurotransmitter metabolism → ↑ dopamine

clinical use for selegiline (l-deprenyl)

cognitive dysfunction — response may take up to 30 days

examples of tricyclic antidepressants

• clomipramine

• amitriptyline

tricyclic antidepressants mechanism of action

• block reuptake of serotonin and noradrenaline (norepinephrine)

• anticholinergic (urine or fecal retention)

• antihistaminic (sedation)

how are amitriptyline and clomipramine different?

both are non-selective SRIs

• clomipramine

  • targeted:

    • serotonin (more selective for serotonin compared to norepinephrine)

    • norepinephrine

    • antimuscarinic, antihistaminergic, anti-adrenergic

• amitriptyline

  • more widespread effects

    • serotonin, norepinephrine, antimuscarinic, antihistaminergic, anti-adrenergic

tricyclic antidepressants side effects

• GI upset

• CNS excitement or seizures

• anticholinergic actions

• cardiovascular toxicity

tricyclic antidepressants drug interactions

• metabolized by CYP450 → enzyme activity can be affected by other drugs

• interactions with other serotonergic drugs

example of selective serotonin reuptake inhibitor

fluoxetine

• reduces reactivity & impulsivity

• reduces fear and anxiety in some dogs

• improves trainability

SSRI mechanism of action

selectively blocks serotonin reuptake

SSRI side effects

• mild sedation

• GI upset

• paradoxical restlessness

• excitement, seizures

SSRI drug interactions

• potent inhibitors of CYP enzymes (fluoxetine)

• do not give concurrently with MAOIs & tricyclic antidepressants

buspirone mechanism of action

• partial agonist at postsynaptic serotonin receptors

• full agonist at presynaptic 5-HT₁A receptors (regulating serotonin release)

indications for benzodiazepine use

situational anxiety — short duration of action

• (potentiate effects of GABA)

trazodone mechanism of action

• serotonin agonist reuptake inhibitors (SARIs)

  • agonist (blocks) serotonin receptors

  • inhibits serotonin reuptake

• antagonism of histamine and alpha-1 receptors

  • sedative/hypnotic effect

  • low to moderate doses

  • immediate calming

indications for trazodone use

situational calming behavior

• dogs — post-op confinement or hospitalization-associated stress

• cats — reduction in transport and examination-related stress

gabapentin/pregabalin mechanism of action

inhibits voltage-gated Ca²⁺ channels in the amygdala → inhibit glutamate release — reduces excitatory neurotransmission

• amygdala — activates sympathetic nervous system, initiating fight or flight response

indications for gabapentin/pregabalin use

• healthy cats

  • pre-treated prior to transport to DVM office

  • improved compliance scores

    • carrier transport

    • DVM examination

dexmedetomidine (oromucosal gel) mechanism of action

• alpha-2 adrenergic agonist

  • pre-synaptic alpha-2 receptors in locus coeruleus (brainstem region governing wakefulness)

• inhibits release of norepinephrine

  • reduce sympathetic response

  • analgesia

  • sedation

dexmedetomidine (oromucosal gel) adverse effects

• bradycardia

• hypotension

• ataxia

• sedation