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Lecture 10

PSYT 301 Lecture Notes - Lecture 10: Dopamine Receptor D3, Nucleus Accumbens, Muscle Relaxant


Department
Psychiatry
Course Code
PSYT 301
Professor
Kathryn Gill
Lecture
10

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Lecture 10: Neurobiology of nicotine; pharmacological effects of nicotine
- Dopaminergic drugs are often abused more frequently than ones that might be
seratogenic
- LeFoll et al. 2003 - Dopamine and sensitization: disruption of nicotine conditioning by
dopamine D3 receptor ligands
- found that repeated injections in the same environment produced
sensitization (amount of activity)
- nicotine preferentially increased DA levels in the shell region of the nAc
(ventral striatum)
- same dose of nicotine was found to stimulate the same amount of locomotor
activity
- conditioned cues from the mouse (expecting the drug) leads to
hyperactivity
- Conclusion: environment that drug is done is crucial to seeing the effects, cue
alone are highly influential in determining the high activity of the animals
- receptor autoradiography showed that there was higher D3 receptor
binding in the nAc shell in the nicotine treated animals
- D3 receptor binding was significantly increased in rats exposed to the
nicotine-paired environment
- found that repeated nicotine in a specific environment, produced
progressive increases in locomotor activity in rats, this is called
context-dependent behavioural sensitization
- sensititization was accompanied by increased d3 receptors
- Nicotine is metabolised to cotinine by the cytochrome CYP-2A6 enzyme (comes in
multiple allelic forms)
- inhalation is one of the fastest ways for the uptake of nicotine, one reason why
patches aren’t as effective is due to the fact that patches are long uptake
- rapid metabolism of nicotine, equilibrate their need for smoking by when the
nicotine plasma levels drop
- acute low dose effects of nicotine
- arousal/pleasure: increased attention, enhanced vigilance, improved
concentration, task performance
- muscle relaxation: nicotine acts on Renshaw cells in the spinal cord which
inhibit motor horn cells, leading to an decrease in motor reflexes, skeletal
muscle relaxation
- heart rate and respiration: excitation at sympathetic cardiac ganglia,
stimulation of chemoreceptors in carotid and aortic bodies leading to reflexive
vasoconstriction, tachycardia, elevated BP
- increased catecholamine release: stimulates chemoreceptors in medullary
centre, increased ACTH and cortisol, increased lipolysis and free fatty acids,
epinephrine release from adrenals increases cardiac output and BP
- someone might develop tolerance over day, lose the tolerance overnight then
withdrawal in the morning
- as nicotine dose increased, stimulatory effects (short acting) were observed more
frequently and powerfully same with pleasurable effects, compared to saline solution
(placebo)
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