Neuroscience Drugs & Behavior- Exam 2

Small Molecule Neurotransmitters

amino acids, monoamines, acetylcholine

Neuropeptides

endogenous opioids

Glutamate

excitatory neurotransmitter

- depolarizes the postsynaptic membrane

- EPSP

GABA

inhibitory neurotransmitter

- hyperpolarizes the postsynaptic membrane

- IPSP

What determines if the amnio acid neurotransmitter is excitatory or inhibitory?

depends on the receptor

Glutamate produces EPSP

influx of sodium ions (sometimes calcium as well) makes the inside of the cell more positive

GABA produces IPSP

influx of ligon gated chloride ions makes the inside of the cell more negative

First neurotransmitter discovered

acetylcholine

Acetylcholine

excitatory at neuromuscular junctions, autonomic nervous system synapses, and important neuromodulator in the brain

Deactivation of Acetylcholine

Ach is degraded in the synaptic cleft by acetylcholinesterase (AChE)

Acetylcholine Esterase

breaks down acetylcholine

Serotonin

indoleamine; 5- HT

- important role is sleep wakefulness and depression and anxiety

Serotonin Degradation

reuptake, monoamine oxidase (MAO)

Prozac

prevents serotonin reuptake and prolongs neural responses to serotonin release

Dopamine, Norepinephrine, Epinephrine

catecholamines

- are removed by reuptake and enzymatic degradation

Degradation of catecholamines

reuptake by active transporter (DA or NE); monoamine oxidase (MAO enzyme)

Diffuse Modulatory Systems

these neurotransmitters are synthesized by a relatively small set of neurons, which have diffuse projections from this central core to multiple regions of the brain

Neuropeptides

roles in modulating emotion, pain, stress, homeostasis

Neuropeptides- Opioids

named because they bind the same receptors that are activated by opium

- endorphins, enkephalins, dynorphins

- co- localized by GABA and serotonin

- tend to be depressants

- act as analgesics, control pain

- addictive, agent of abuse

Drugs

exogenous

Transmitters

endogenous

Goal of modern psychopharmacology

develop drugs with high specificity and low toxicity

Pharmacodynamics

study of the physiological and biochemical interaction of drug molecules with cell receptors in target tissue

Agonists

substance that INCREASES the effectiveness of a neurotransmitter

Antagonists

substance that DECREASES the effectiveness of a neurotransmitters

Agonists

promote neurotransmitter release

Antagonists

decrease or block neurotransmitter release

Agonists

stimulate receptors; bind to the postsynaptic receptors and open transmitter-gated ion channels

Antagonists

block receptors; bind the postsynaptic receptors and prevent opening of transmitter-gated ion channels

Degradation in Agonists

inhibit degrading enzyme, block reuptake

Drugs that bind to a neurotransmitter's auto receptors without activating them are usually?

agonists

Nicotine

acts as an agonist and stimulates cholinergic receptors

Botulin toxin (botox)

is the poisonous agent found in tainted food and it inhibits the release of Ach and therefore is an antagonist

Physotigmine

is a drug that inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine

- physostigmine therefore acts as an agonist to increase the amount of Ach available in the synapse

Drug action

molecular changes produced by a drug when it binds to a target site or receptor

Drug effects

the physiologic/ behavioral reactions of the body to a drug

Therapeutic effects

the drug-receptor interaction produces desired physical or behavioral changes

Which of the following examples best illustrates a side effect?

nausea and dizziness experienced after starting a new medication

Bioavailability

amount of drug in the blood that is free to bind at target sites

Pharmacokinetic component of drug action:

the dynamic factors that contribute to bioavailability

Routes of Administration

the way that a drug enters and passes through the body to reach its target

To bypass the blood- brain barrier:

injection in the cerebro-spinal fluid or directly in the brain

The route of administration affects

the dosage of the drug

Absorption

movement of the drug from site of administration to the blood circulation

Blood- Brain Barrier

capillaries that selectively let certain substances enter the brain tissue and keep other substances out

Drug Depots

binding at inactive sites where no biological effect is initiated

- drug molecules tied up in these depots cannot reach active sites or be metabolized by the liver, but binding is reversible

Half- life

amount of time required for removal of 50% of the drug

- determines interval between doses

Metabolism

the process of destructing drug molecules

- drugs are broken down in the kidneys, liver, and intestines

Excretion

the processes of eliminating waste products

- drugs are excreted in urine, feces, sweat, breast milk, and exhaled air (urine is most important)

Psychoactive drugs

produce an altered state of consciousness

Drugs of abuse

stimulants, depressants, opioids, hallucinogens, inhalants

Drug misuse/ abuse

the use, generally by self-administration, of a drug in a way that deviates from the social norms of a given culture

Drug tolerance

diminished response to a drug after repeated exposure

Cross tolerance

tolerance to one drug can diminish effectiveness of a second drug

Metabolic tolerance

increase in number of enzymes used to break down substance

- decrease in drug bioavailability

Pharmacodynamic tolerance

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

- examples: receptor down- regulation and up- regulation

Behavioral tolerance

people learn to cope with being intoxicated

Withdrawal

sudden cessation of drug use

- using drugs over and over again and then you suddenly stop

Withdrawal symptoms

- sweating

- shaking

- nausea/ vomiting

- sleeplessness

- anxiety

- loss of appetite

What is the relationship between drug tolerance and withdrawal?

tolerance can lead to heightened withdrawal symptoms

Sensitization

enhancement of drug effects after repeated administration of the same dose

Drug dependence

pattern of use in which the individual perceives the need to continue usage

Physical dependence

overt symptoms

Psychological dependence

drug craving

Drug addiction

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

Drug reward

positive experience associated with the drug

Self Brain Stimulation

Median Forebrain Bundle, VTA, Prefrontal cortex, Nucleus Accumbens

Median forebrain bundle

group of axons start in the VTA

Ventral tegmental area

a group of dopamine-containing neurons

Nucleus Accumbens

a subcortical structure that participates in reward and addiction

Which of the following statements accurately describes animal experiments on reward in self- brain stimulation?

animals demonstrate a strong preference for self- stimulation, often over natural rewards

Mesolimbic Dopamine System

Dopamine from the Midbrain to the Limbic System

- increase in dopamine release with natural rewards

Drug self- administration

Nucleus accumbens, Ventral tegmental area

How do drugs affect our bodies?

Alter normal functioning of these systems (Limbic and Neurotransmitters)

- increase in synaptic activity

Current view

overt physical symptoms and psychological cravings are all manifestations of neuroadaptation

In addition to important changes in the dopamine system,------- from synapses in the -------- appears to be involved in the development and persistence of addiction

glutamate, nucleus accumbens

Why do some people become addicted while others do not?

vulnerability

Commonly used forms of cocaine

powder, freebase cocaine, crack

Powder

- purified directly from coca leaves

- can be cut with other white powders

Freebase cocaine

if cocaine is treated with various chemicals, it can be isolated in a chemically "free" form that is more readily smoked

Crack

- solid chunk of cocaine

- prepared by boiling the powdered form with sodium bicarbonate (baking soda)

Routes of Absorption

ingestion, snorting powder, inhaling cocaine from heated crack

Ingestion

such as chewing is not very effective, in part because the liver degrades the cocaine before it ever reaches the brain (first- pass metabolism)

Snorting Powder

- relatively slow way to get cocaine in to the bloodstream (relative to inhalation or IV)

- blood levels rise relatively slowly, peaking after 30-60 mins

Inhaling cocaine from heated crack

the cocaine is delivered to the bloodstream nearly as quickly as if injected

- peak blood levels occur within several minutes are much higher than similar dose of snorted powder

- high only lasts ~ 30 mins

Cocaethylene

is formed in the body when cocaine and alcohol are used together

Behavioral effects of cocaine

increased movement and psychotic like states (delusions, hallucinations)

Cocaine via injection or smoking: "The Rush"

a feeling of intense physical pleasure, euphoria, great self- confidence and well-being

Cocaine if snorted or taken orally

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

Increased movement

constant motion: talking, moving, exploring, fidgeting

- affects the basal ganglia

- at higher doses, the movement becomes more focused and repetitive

Psychotic- like state (delusions, hallucinations)

- this happens at very high doses and/ or after prolonged use

- resembles psychotic schizophrenia

- can occur at the end of the several- day binge when blood levels are very high

Cocaine increases synaptic dopamine levels by

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

Cocaine also increases frequency of dopamine release

it inhibits NE uptake in the PFC, causing an NE receptor- mediated stimulation of glutamatergic neurons that project to the VTA

At higher concentrations, cocaine also blocks voltage- gated NA+ channels

leads to a local anesthetic effect

Which of the following contributes to the increase in NAc dopamine caused by cocaine?

Inhibit of DA reuptake, inhibitions of NE reuptake

Amphetamine

typically taken orally or IV or subcutaneous injection (skin popping)

- absorption from the GI tract is slow

- IV injection provides a rapid and intense "high"; has much greater addictive potential

Methamphetamine

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

- methamphetamine hydrochloride in a crystalline form suitable for smoking is called "ice" or "crystal"; highly addictive

Behavioral effects of amphetamines

- heightened alertness

Increased confidence

- feelings of exhilaration

- reduced fatigue

- generalized sense of well- being

- reduced sleep time, especially REM sleep; - permits sustained physical effort without rest or sleep

- can enhance athletic performance; banned in competitions

Amphetamines are indirect catecholamine agonists

they stimulate DA and NE release and block reuptake

Amphetamine and methamphetamine have therapeutic uses:

- narcolepsy

- ADHD

- appetite suppressant and anti obesity treatment