Dopamine Function And Addiction Flashcards
How do amphetamines work?
Increase release and decrease uptake via reversal of the uptake pump
Inhibits dopamine breakdown via MAO inhibition
What does high dose of systemic amphetamines dots a mouse?
Causes sterotypy - complex movements which are not goal directed)
What does low dose amphetamines cause in mice?
Hyperactivity
What are the possible explanations for dose dependanct reactions for amphetamines?
Larger release in dopamine within the NAc than striatum
Competition between behaviours
What behaviour is produced by amphetamines injection into the NAc?
Hyperactivity
What is the effect of amphetamine injection in the striatum?
Stereotypy
What is the explanation for hyperactivity as a result of amphetamines?
Environment has become more salient due to increas ein dopamine - manifestation of urge to explore new environment
What is operant conditioning?
Animal wil repeats behaviour is the consequence is rewarding e.g. Food, sex, water (driven by motivation)
IN the Skinner box what causes an increase in dopamine?
Receiving a reward or a stimulus which has previously been associated with the reward
What is the effect of a dopamine antagonist (Pimozide) on number of lever pressings on test days following conditioning?
They will decrease
What will happen to number o levers presses of no reward is given after conditioning?
They will decrease
What is the process by which an animal will decrease the number of times it presses the lever?
Extinction
What is self stimulation?
Animals will work to receive an electrical stimulus of certain brain areas
What areas are most effective for promoting self stimulation?
Ventral tegmental area
Median forebrain bundle (pathway between VTA and nucleus accumbens)
What other areas (to a lesser extent) will animals self stimulate?
Prefrontal cortex
Nucleus accumbens
What are the factors which influence self stimulation?
Drugs/ lesions
What can be used to lesion areas containing tyrosine hydroxlase
6-OHDA
What does 6-OHDA do when applied to NAc?
Blocks hyperactivity
What is the effect on self stimulation on modification of applied current?
Self stimulation is not supported below a certain threshold
As the current increases so will press rate
What occurs to press rate on lesions of the median forebrain bundle?
It will be abolished
What will happen to press rate on self stimulation on low dose dopamine antagonists?
It will decrease i.e. Pressing lever will have a smaller effect therefore will not do as often
What will happen to threshold current on addition of dopamine antagonists?
It will increase. I.e. Current which would normally support self stimulation will increase
What is self administration?
Animals will work to receive drug infusions IV or intra cerebrally
What drugs will be self administrated intravenously?
Cocaine Amphetamine Ethanol Morphine Nicotine
What drugs will be administered locally for promote self admin?
Amphetamine into the NAc
Morphine into the VTA
What factors influence the self administration of cocaine and amphetamine?
Potentiated by dopamine antagonists i.e. Will work harder to overcome blockage of receptors @ low doses of antagonists. At high doses of antagonist all receptors will be block thus behaviour will be attenuated
What else attenuates self administration?
6-OHDA lesions of the NAC
What is conditioned place preference?
Rats will go to chamber where they receive a reward
After condition get a particular chamber with a reward what will happen when a rat is placed into the chamber again? (Without reward)
Rat will go back to chamber where it received the reward. Can measure % time spent in either chamber (old reward chamber vs non reward chamber)
What rewards will cause the rat to increase time spent in reward chamber?
Amphetamine
D1/D2 agonists
Food (amphetamine will enhance the reinforced behaviour)
What other things can cause an increase in dopamine within the NAc?
Adverse stimuli e.g. Mild food shock
Release on stimuli predictive of either an adverse or rewarding stimuli
What does dopamine increase in the NAc signal?
The salience of a stimuli. Useful for learning. For example, if you find food under a certain type of tree, seeing that tree will increase dopamine level and drive the motivation to eat. Like wise, if a certain see if predictive of a predator seeing that tree will elicit an increase in dopamine
How do drugs effect dopamine?
Of the drugs a mouse will self administer all increase dopamine directly or indirectly (NAc>dorsal striatum)
All have addictive properties
Why is it hypothesised that it is the potentiation of dopamine in the NAc which causes addiction?
The drugs all have different effects e.g. Some are stimulants, hallucinogens and others are depressants. Therefore, their addictive properties are unlikely to be related to their primary pharmacology but their ability to increase dopamine in the NAc
what is a common property of addictive drugs?
Increase self stimulation
Support self administration
Show conditions place preference
Enhance reinforced behaviours
What do addictive drugs do?
‘Hijack’ the physiological reward/salience pathway which signals if things are pleasurable or important. This system is essential for reinforcing behaviours of importance
What can stimuli associated with drugs do?
Stimuli like watching another person take drugs or seeing a needle will make the person want to take the drug = dependency
What are the signs and symptoms associated with dependency?
Withdrawal Interests (decrease) Tolerance Harmful consequences Desire/compulsion Control of intake decreases
Overall wha tis the function of dopamine in the NAc?
Reinforce behaviours which are associated with pleasurable or adverse events through release of dopamine in response to salient stimuli
