Neuroscience studying

Drug tolerance

Diminished response to a drug after repeated exposure

cross tolerance

TOlerance to one drug can diminish effectiveness of a second drug

Types of tolerance

metabolic, pharacodynamic, behavioral

Significant characteristics of tolerance

reversible when drug use stops, dependent on dose and frequency of drug use and enviornment, may occur rapidly, not all effects of drug show the same degree of tolerance, several different mechanisms explain multiple forms of tolerance

Metabolic tolerance

Increase in number of enzymes used to break down substance, decrease in drug bioavailability

Pharmacodynamic toleracnce

changes in nerve cell function compensate for continued presence of the drug

Behavioral tolerance

people learn to cope with being intoxicated

withdrawal

sudden cessation of drug use

symptoms of withdrawal

sweating, shaking, nausea/vomiting, sleeplessness, anxiety, loss of appetite

Drug addiction is…

the term usd to describe an overall pattern of compulsive drug abuse characterized by consistent preoccupation with drug consumption and a tendency to relapse after withdrawal

The point at which abuse or _ becomes _ is

hazy.

dependence, addiction

natural rewards that elevate dopamine levels are

food and intercourse

how do drugs affect our bodies

they affect the limbic system and neurotransmitters, they increase synaptic activity (dopamine), they alter dopamine activity

The receptors involved with alterations from drugs of dopamine activity are

D2, D3, D4

The brain area that is involved with alterations from drugs of dopamine activity are

nucleus accumbens

All drugs of abuse target the brain’s…

Pleasure center

all drugs of abuse increase…

dopamine

Overt physical symptoms and psychological cravings are all

manifestations of _.

Neuroadaptation

Neuroadaptation is the brain's

ability to adjust its structure, function, and neural pathways in response to new, changing, or repeated stimuli, such as sensory input, substances, or injury

circuits involved in drug abuse and addictions

inhibitory control, motivation drive, memory and learning, reward and salience

dopamine D2 receptors are _ in addiction

lower

lower D2 receptor expressions and lower baseline dopamine release cause

a blunted response to natural rewards such as food and intercourse

addicted subjects dont feel “"_” unless they have their _ increased by drugs

normal, dopamine

epigenetic processes are

reversible chemical modifications to DNA or associated proteins that turn genes "on" or "off" without changing the underlying DNA sequence

synaptic plasticity is

the brain's ability to strengthen or weaken connections (synapses) between neurons over time in response to activity, forming the foundation of learning and memory

in rats behavioral responses to cocaine associated cues increase as

the number of days since the last cocaine exposure increases

in rats behavioral responses to cocaine associated cues are associated with

changes in glutamate signaling in the NAc

Behavioral effects of cocaine via injection or smoking

“the rush” is a feeling of intense physical pleasure, euphoria, great self-confidence and well-being

Behavioral effects of cocaine while snorted or taken orally

the rush feeling is less intense than injection and is more a sense of well-being

behavioral effects of cocaine of increaded movement are

constant motion ( talking, moving, exploring, fidgeting), at higher doses movement becomes repetitive and more focused

Psychotic like state while using cocaine

happens at very high doses or after prolonged use, much like psychotic schizophrenia, can occur after several day binges when blood levels are high

Cocaine increases synaptic dopamine levels by…

binding to the plasma membrane DA transporter and blocking reuptake of the neurotransmitter

Inhibition of DA reuptake can occur

rapidly

at higher concentrations cocaine also blocks

voltage-gated Na+ channels (leads to local anesthetic effect)

An Amphetamine is

taken orally or IV or subcutaneous injection, the absorption from the GI tract is slow, IV injection provides a rapid and intense “high”

Methamphetamine is

more potent than amphetamine, can be taken orally, snorted, injected intravenously, or smoked

Methamphetmine hydrochloride is

in a crystalline form suitable for smoking, highly addictive

Amphetamine and methamphetamine are metabolized

slowly by the liver

metabolites are excreted in the

urine

Because of long _, users obtain a much _ high

from a single dose of amphetamine or methamphetamine than

from a dose of cocaine.

half-lives, longer-lasting

Behavioral effects of amphetamines

hieghtened alertness, increased confidence, feelings of exhilaration, reduced fatigue, generalized sense of well-being, reduced sleep time, enhanced athletic performance, psychosis

amphetamine and methamphetamine Stimulate massive DA release in two ways

Enters nerve terminal by dopamine transmitter, and stimulates dopamine release from vesicles, and alters dopamine transmitter to act in reverse direction to release dopamine to synapse

Amphetamines are indirect

catecholamine agonists, they stimulate dopamine and NE release and block reuptake

NE release also affects

sympathetic nervous system

psychostimulant users showed…

decreased DA synthesis and decreased DA release, less DAT binding, and less DA receptor binding

ADHD is characterized by

extreme inattentiveness impulsivity and hyperkinesis, thought to be related to dysfunction in complex neural circuits that include the PFC

When using a psychostimulant as someone with ADHD they have a seemingly

paradoxical calming effect

Methlphenidate (Ritalin) helps by

activating catacholamine transmission by blocking DAT and NET it increases extracellular levels of DA and NE

Nicotine routes of administration: inhalation

it is vaporized by the heat at the end of a cigarette and it attaches to tiny particles called tar

tar contains many things

it contributes to taste and smell of the smoke

inhaled nicotine reaches the brain in

seven seconds

nicotine is mostly metabolized in the _ and is excreted via the _

liver, kidneys

the body can metabolize most of the nicotine from 1 cigarette in

one to two hours

nicotine and tar induce…

the production of liver enzymes which results increased metabolism of other drugs

nicotine is an _ for _

agonist, nicotine acetylcholine receptors

nicotine receptors are also used to signal

muscles to contract

nicotine effects the _ that responds to the neurotransmitter _

ligand-gated ion channels, acetylcholine

Acute tolerance: brief; due to desensitization of central nAChRs

smokers undergo acute tolerance during the course of a day, after overnight abstinence smokers awaken more sensitive to nicotine than end of the day

Chronic tolerance from long-term exposure:

smokers show an up-regulation of nAChR levels in many brain areas

The transmitter dopamine is produced in the

ventral tegmental area

The transmitter dopamine is involved in,,,

motivation and reward seeking

the pathway dopamine takes is the…

mesolimbic pathway

nicotine reinforcement can be influenced by many factors including

sex and age

aversive effects of nicotine

nausea, dizziness, sweating, headache,

palpitations, stomach ache, and clammy hands

Aversion is dependent on nAChRs containing the…

α5 subunit

Knocking out the α5 subunit _ nicotine self-

administration at _

enhances, high doses

Non-nicotine drugs – most effective with behavioral intervention

Bupropion, Varenicline

Varenicline is a

partial agonist at high-affinity

Bupropion is a

a DA and NE reuptake inhibitor and weak nAChR

antagonist

Caffine is Completely absorbed by GI tract in

30-60 minutes

Average plasma half-life of caffine is

4 hours

Metabolism of caffeine is _

by nicotine and _ by alcohol

increased, decreased

Adenosine is

a naturally occurring purine nucleoside and fundamental component of ATP (energy), RNA, and DNA

Adenosine builds up during wakefulness, creating a state of

drowsiness

Caffeine’s main action on the brain is

to block receptors for the neurotransmitter adenosine