nicotine, caffeine, and karatom pt 2

acute tolerance to nicotine

cigarette smokers undergo acute tolerance over the course of the day

• due to desentization of nictoine receptors

over the course of a day a smoker undergoes

• repeated elevated and drops in plasma membrane levels

• early in the day mood may be elevated above baseline level

• later peaks in nicotine may be only enough to maintain neutral mood and avoid withdrawal symptoms

• nachrs re-sensitize significantly overnight» allows cycle to repeat

  • increase in nicotine is evident of less pleasure

when do withdrawal symptoms in nicotine occur

pump in experiment runs out of nicotine or if receptor antagonist, mecamylamine is given

brain reward function in chronic nicotine use

reduced during withdrawal

• increased threshold for ICSS

withdrawal symptoms are mediated by what

are mediated by reduced DA actvitiy in NACC and increased CRF in amygdala

DMS5 definition of tobacco use disorder

nictoine abuse disorder is also dictated by what other factors

sensory stimuli associated with the act of smoking

• i.e. actually holding the cigarette etc

• denic puffs had the highest

nicotine replacement therapy (NRT)

• relieves withdrawal symptoms

• delivered in a safer way than smoking

• NRT helps smokers quit 50%- 60% compared to placebo or no intervention

bupropion

antidepressant

dopamine and NE reuptake inhibtor

similar structure to stimulants

reduces cravings and withdrawal symptoms

chantix or varnicline

partial agonist of alpha 4 beta 2 nicotinic receptors

• produces a moderate amount of receptor activation

• reduces nicotine cravings and adverse withdrawal symptoms

• more effective than buproprion

caffeine

from coffee means, consumed orally, converted to metabolites by CYP1A2

fours hour half life

paraxantine

metabolite of caffeine

cns stimulant

further breakdown leads to metabolites that are secreted in the urine 95% are eliminated trough the urine

lab animals bisphaic effects low

stimulant effects

lab animals bisphasic effects

show reduced activity

low doses in humans of caffeine

positive subjective effects

feeling of well being, increased energy, increased alertness, enhanced sociability

high doses humans of caffeine

anxiogenic

people with panic disorder are hypersensitive to caffeine’’s anxiogenic effects

cognitive effects of nicotine

increased blood pressure, heart rate, increased urine output

chronic caffeine use leads to

tolerance

caffeine withdrawal

sleepiness, headache, and irritability

intense craving

acute caffeine intake physiological effects

increase BP

increased respiration rate

enhance water excretion

caffeine intoxication

restlessness nervousness, insomia, tachycardia, muscle twitching, GI upset

hard to distinguish to generalized anxiety disorder

3 to 5 g cause death

therapeutic uses of caffeine

potentiates analgesic properties of aspirin and acetaminophen

included in some OTC pain medications (Anacin and Excedrin)

effective in treatment of apnea in premature newborns because it regularizes breathing

epidemological studies of caffeine

caffeine biochemical effects

Inhibition of cAMP phosphodiesterase (PDE)

Blocks GABAA receptors

Stimulates Ca2+ release within cells

Blockade of A1 and A2A adenosine receptors

toxic doses effects of caffeine

Dose-dependent inhibition of cAMP phosphodiesterase, blockade of GABAA receptors

stimulation of Ca2+ release in cells

complete blockade of A1 and A2A receptors and operate at doses

acute does a partial blockage of A1 and A2A receptors

adenosine

NT that promotes sleep

caffeine and adenosine

caffeine antagonizes adenosine

caffeine and DA

caffeine removes break on DA signaling

adenosine and DA

adenosine receptors A2A receptors are coexpressed with post synaptic D2A receptors to form heterotetramers

adenosine allosterically inhibits D2R receptors signaling

evidence of caffeine and DA

In striatal neurons, A2AR agonists decrease D2R agonist binding>>decrease affinity of DA for its receptor • caffeine-induced increases in locomotor activity and arousal are absent in A2AR KO mice

Kratom

tree found in Southeast Asia

low doses act like stimulant

high doses act like narcotic or sedative

used to self-treat conditions such as pain, coughing, diarrhea, anxiety and depression, opioid use disorder, and opioid withdrawal

kratom

does not resemble typical opioids and isn’t scheduled