Hbd1: Neurophysiology Of Drug Addiction, Karius

Front 1

A drug addiction is characterized by at least 3 of these things

Back 1

Tolerance

Withdrawl

Craving

Use of the drug in larger amounts than intended

Considerable time invested

Continued use despite health, social, or economic problems

Front 2

Effects of addictive drug on the taker

Back 2

Euphoria
Reinforcement
Tolerence (pharmacological, i.e.altered metabolism and pharmocodynamic, i.e. altered neuronal response)
Sensitization (inc. effects w/ repeated dose)
Cravings

Front 3

Take home message for the neurophysiology of Drug addiction?

Back 3

Activation of normal neurophysiological events by the drugs of addiction (pleasure/rewards system and the changes associated w/ memory and learning)

Front 4

Core of the reward/pleasure system

Back 4

VENTRAL TEGMENTUM AREA(VTA)and the Nucleus Accumbens (third part of basal ganglion)

Front 5

Nucleus accumbens micro-circuitry and Histology

Back 5

Same as the others of the basal ganglion w/ direct and indirect pathways

Histo - Core and shell region (each plays a distinct role in pleasure)

Front 6

Median forebrain bundle

Back 6

The path by which the nucleus accumbens (NAc) recieves input from the VTA

Front 7

Neurotransmitter released onto NAc from the VTA, receptor it binds to and its effect

Back 7

Dopamine released onto a D3 receptor and causes inhibition

Front 8

The ventral tegmental area receives excitation from...

Back 8

Prefrontal cortex - EAA

Lateral Hypothalamus - Orexin

Laterodorsal Tegmental Nucleus - EAA

Front 9

Inhibition of the VTA

Back 9

Through an internal circuit in the VTA via GABA-ergic VTA neurons

Front 10

The release of Dopamine from the VTA is controlled by...

Back 10

an integration of both excitatory and inhibitory influences

Front 11

What receptors do the dopaminergic NAc neurons express?

Back 11

GABA receptors

Front 12

Excitatory inputs onto the NAc

Back 12

Prefrontal cotex
Amygdala
Hippocampus
(all using EAA)

Front 13

NAc neurons release this Neurotransmitter onto their targets

Back 13

GABA

Front 14

What is the effect of dopamine release onto the NAc?

Back 14

Decreases the release of GABA by NAc neurons allowing activity of the rewards pathway

Front 15

Where is output from the NAc?

Back 15

Prefrontal cotex and VTA (co-transmitter dynorphin is released w/ GABA)

Front 16

What are the non-endogenous pleasure/reward systems inputs?

Back 16

opioids (also activate locus ceruleus and periaquaductal grey)

Front 17

Purpose of reward/pleasure system?

Back 17

reinforce the occurrence of certain behaviors important for survival

Front 18

What type of feed back system is Pleasure/rewards system?

Back 18

Positive

Front 19

The production of memory is very close and may overlap what other system

Back 19

rewards/pleasure

Front 20

What is the main mechanism by which memory is created

Back 20

Long term potentiation (LTP), associated w/ CREB and changes both pre and postsynaptically (inc. NT)

Front 21

MOA of Opiates

Back 21

Agonist at opiod receptors (u, k and sigma)
second messanger system

Front 22

MOA of cocaine

Back 22

inhibits re-uptake of dopamine...inc. dopamine at synapse

Front 23

Amphetamines MOA

Back 23

activation of dopamine inputs

Front 24

Nicotine MOA

Back 24

Agonist at nicotinic cholinergic receptors in the VTA...influx of Na...release of Dopamine

Front 25

Cannabis MOA

Back 25

CB-1 receptor...leads to dopamine release

Front 26

MOA of Ethanol

Back 26

Increases GABA receptor Function, decreases NMDA receptor function
activates the opiod inputs (Particularly VTA)
Disrupts EAA from the prefrontal cortex to the NAc

Front 27

PCP MOA

Back 27

Antagonist at NMDA receptors, blocks Ca channel
Disrupts EAA inputs to the NAc from the prefrontal cotex

Front 28

Action of increased dopamine in the NAc

Back 28

Euphoria is produced

Front 29

LTP has been shown to occur in the VTA dopamanergic neurons in response to 2 drugs

Back 29

Cocaine and nicotine

Front 30

What effect does blocking the NMDA receptor in the VTA cause

Back 30

blocks some of the effects of the addictive drugs: self administering drug, behavioral sensitization, and conditioned place preference

Front 31

Long term changes in the neurons as a result of addictive drugs

Back 31

Induction of CREB (cyclic-AMP response element binding protein), it is part of the regulatory region in many genes

Front 32

How does CREB produce effects of drugs?

Back 32

W/in the NAc you get an inc. production of dynorphin (opiod) binds to k-receptors

Front 33

How does desensitization result

Back 33

NAc turns the input from the VTA off reducing the effects of the drugs

Front 34

Input that the NAc sends to the VTA

Back 34

both GABAergic and dynorphin-ergic input

Front 35

Physical dependence on a drug is the result of?

Back 35

Activation of CREB in the periaquaductal grey and locus cereleus

Changes in CREB are temporary lasting about a week

Front 36

role of delta-FosB

Back 36

long term response to drug addcition

Front 37

How does sensitization result

Back 37

W/in the NAc Delta-FosB leads to inc. expression of AMPA subunit GluR2...causes reduced excitation of these neurons (e.g. from EAA)...renders them more sensitive to Dopamine's influences