Psychopharm Quiz 6 - Nicotine and Caffeine

in smokers, nicotine produces a

a calm or relaxed state, partly as relief from nicotine withdrawal symptoms

nicotine administration to nonsmokers tends to elicit

heightened tension or arousal, along with lightheadedness, dizziness, and even nausea

because ACh plays an important role in aspects of cognitive functioning,

several studies have examined effects of nicotine on cognitive function

Abstinent smokers given nicotine show enhanced

function on cognitive and motor tasks

Many studies have concluded that nicotine has a positive

influence on cognitive and motor functioning even in nonsmokers (Hahn 2015)

High smoking rates in people with cognitive disorders such as ADHD may be an attempt to

medicate their cognitive impairment with nicotine

In one study, non-smoking college students were prescreened and divided into low-attention and high-attention groups

Results supported the hypothesis: Nicotine significantly increased scores in the low-attention but not the high-attention group

nicotine use for alzhiemers

Patients showed increased capacity for learning verbal material following nicotine use

nicotine use for parkinsons

neuroprotective for dopamine neurons

nicotinic receptors are abundant in

the ANS

smoking can activate both the

sympathetic and parasympathetic systems, causing a wide range of physiological effects, including tachycardia and elevated blood pressure.

smoking can raise the risk of

cardiovascular disease

nicotine reduces

appetite and increases metabolic rate, resulting in weight loss

nicotine is a toxic substance that can be fatal at

high doses, with most of the nicotine in cigarettes lost in burning of the tobacco or sidestream smoke

Accidental poisoning can result from swallowing nicotine

(mostly by children), contact with tobacco in the field, or insecticides that contain nicotine

during the night, mild nicotine withdrawal occurs

but at the same time, tolerance from the previous day dissipates

The individual awakens the next morning with a strong craving for a cigarette but also may

experience the strongest or best response of the day

Acute tolerance is related to desensitization of central

nAChRs, including those that mediate nicotine reinforcement

long-term exposure to nicotine causes

chronic tolerance, superimposed on the acute within-a-day tolerance

The subjective effects of nicotine, both rewarding and aversive, are most susceptible to

chronic tolerance in smokers

Chronic tolerance is surprisingly slow to dissipate, even after prolonged abstinence

nicotinic receptor desensitization is generally thought to be the primary mechanism

Chronic exposure to nicotine elicits a compensatory response

an up-regulation of high-affinity nAChR expression in many parts of the brain

Smokers have substantially lower levels of

MAO activity in the brain and peripheral organs

PET scans show MAO-B inhibition in

various organs of a smoker compared to nonsmoker

MAO is important in the breakdown of

dopamine; MAO inhibition may contribute to the reinforcing effects of smoking

long nicotine withdrawal leads to

complex abstinence syndrome, which includes affective and somatic symptoms

affective symptoms

anxiety, irritability, depressed mood, anhedonia, insomnia, restlessness, hyperalgesia

somatic symptoms

tremors, bradycardia, nausea, hunger and weight gain

abstinence syndrome is mediated by a combination of

1. Resensitization of the desensitized and up-regulated nAChRs

2. Reduced activity of the mesolimbic dopaminergic pathway.

nicotine resource model

Smokers routinely report that smoking causes relaxation, alleviation of stress, and increased ability to concentrate

deprivation reversal model

positive effects of smoking represent alleviation of irritability, stress, and poor concentration experienced by smokers between cigarettes

other factors are involved in nicotine dependence

Sensory stimuli associated with the act of smoking become conditioned to the reinforcing effects of nicotine and thus function as secondary reinforcers

Recent research shows that smoking produces epigenetic effects

changes in DNA methylation on over 1000 genes

Chemicals in cigarette smoke pass through the placenta to

reach all organs of the developing fetus, including the brain

Animal studies show that prenatal exposure has long-lasting deleterious effects on

somatic and neurobehavioral development

Animal studies have shown that nicotine exposure leads to long-term neural changes and various behavioral effects in adolescence

including attention deficits, impulsivity, and increased self-administration of abused drugs

e-cigs are now the main route for nicotine exposure

and have potential for inducing nicotine dependence in young people who might otherwise not have taken up tobacco smoking

There is some evidence that young adult e-cigarette users are more likely to

start using tobacco cigarettes than those who were not e-cigarettes users

The argument for e-cigarettes is based on the notion that they are

much safer than tobacco cigarettes, and are a healthier substitute; fewer chemicals in e-cig vapor

nicotine treatments include

behavioral interventions and nicotine replacement theory

nicotine behavioral interventions

Individual/ group counseling with social support/ training/ coping skills

nicotine replacement theory

Deliver nicotine in safer way than through smoking/ chewing tobacco

wellbutrin

antidepressant that inhibits reuptake of DA and NE, weak nAChr agonist

chantix

Partial agonist for nAChR expressed in the VTA and other brain areas, elicits moderate receptor activation and reduces cravings/adversive effects

major source of caffeine is

coffee beans, the seeds of the plant Coffea arabica

tea leaves contain

caffeine and related compound theophylline

Caffeine and theophylline are members of a group of plant-derived chemicals called

methylxanthines, includes theobromine

caffeine route of admin

typically oral

caffeine absorption

Completely absorbed from GI tract (across intestinal walls) in 30 -60 min

repeated coffee drinking throughout the day

increases plasma caffeine levels gradually

caffeine distribution

throughout brain and body with no accumulation in body; readily passes BBB

caffeine is broken down in the liver into

active metabolites

the rate of caffeine plasma clearance is stimulated by

smoking and reduced when smoking ends; resulting increase in plasma caffeine levels could contribute to cigarette withdrawal symptoms in heavy coffee drinkers

Caffeine Excretion

first order, with a half life of 4-6 hours

caffeine excretion in urine

95% as metabolites and 5% unchanges

neurons use glucose as source of fuel, so when glucose is low they look to

astrocytes, which provide glucose by mobilizing glycogen from storage and produces adenosine

adenosine

inhibitory neurotransmitter that makes people sleepy

caffeine is an antagonist for

adenosine receptors (4 types)

A1 and A2A receptors mediate most of

adenosine's effects in the brain and are the major targets of caffeine

a primary location of A2A receptors is in

the GABAergic output neurons of the dorsal striatum (caudate-putamen) and ventral striatum (NAcc), which are also rich in DA receptors

the blockade of adenosine receptors, particularly the A2A subtype

underlies caffeine-induced behavioral stimulation

caffeine does not bind to

dopamine receptors

Adenosine receptors form complexes with

DA D2 receptors, with adenosine stimulation blocking DA receptor activation

Blocking adenosine receptors enhances DA receptor signaling

leading to mild arousal and psychomotor activation

Pituitary gland responds to increased neuronal firing

assumes there is an emergency and releases hormones to periphery, telling adrenal glands to produce epinephrine & activate sympathetic nervous system

caffeine activates the sympathetic NS by

increasing heart rate, increases blood pressure by constricting cerebral arteries, and acts as a coronary artery vasodilator & bronchodilation

adenosine receptors found in the kidneys and heart

acts as a diuretic

Acute caffeine intake leads to several physiological effects

including increased blood pressure and respiration rate, enhanced water excretion (diuresis), and stimulation of catecholamine release from the adrenal medulla

Daily caffeine consumption up to 400 mg poses little or no risk to healthy individuals

increases mental performance and endurance, delays fatigue, and improves migraine symptoms if taken onset

Recent research suggests acute caffeine effects are not just due to alleviation of withdrawal symptoms

In a test of cognitive measures on caffeine consumers and nonconsumers, both groups benefitted significantly from the caffeine treatment

caffeine intoxication

associated with recent high-dose caffeine use (1000 mg or more); characterized by restlessness, nervousness, insomnia, tachycardia(increased heart rate), muscle twitching, and GI upset

3-4 cups per day has some protective effect against development of

type 2 diabetes, with decaff producing the same effects other constituents such as chlorogenic acids may be the active substances.

coffee potentiates analgesic properties

of aspirin and acetaminophen. It is included in some OTC pain medications

Coffee may reduce risk for some cardiovascular diseases, but

increase risk for others, especially in people who are slow caffeine metabolizers.

Lifelong coffee/caffeine consumption reduces risk of developing

Parkinson's and other age-related cognitive decline

actions of caffeine include

blockade of GABAA receptors, stimulation of Ca2+ release within cells, and blockade of A1 and A2Areceptors for adenosine

At levels of caffeine in one or a few cups of coffee

only adenosine receptors are blocked

ethanol consumption increases adenosine

caffeine prevents activation of adenosine, masking alcohols sedative effects (hyper drunk)

Mild dependence seen in individuals chronically using >100 mg/ day

with caffeine dependence not recognized as substance of abuse by DMS-5

caffeine tolerance

variable among users and high doses of caffeine may produce complete tolerance in some individuals