Addiction Lecture 1

Question 1

The release of __ in the ___ reinforces behaviour.

Answer 1

DA (dopamine) in the (NA) nucleus accumbens

Question 2

What is the biochemical evidence for the hypothesis that simulation of __ transmission in the ____ system might be a fundamental property of drugs of abuse?

Who did the study?

What happened to drugs that were aversive?

Answer 2

Dopamine transmission in the mesolimbic system might be a fundamental property of drugs of abuse.

Di Chiara and imperato 1988 studied the effects that drug of abuse had on dopamine release in the nucleus accumbens of rats. They did this by inserting microdialysis probes into their NA. All euphoric drugs e.g. morphine, heroin, ethanol, nicotine caused a release of DA in the NA.

Drugs that were aversive e.g. agonists of the K opioid receptor decreased dopamine release in the NA which led to dysphoria.

Question 3

Drugs of abuse increase __ levels in the __ by either:
1)
2)

Answer 3

Dopamine levels in the Nucleus Accumbens (Nacc)

1) Increasing firing rate of dopamine neurones
2) Inhibiting dopamine reuptake

Question 4

How do opiates work?

Answer 4

They act on Mu opioid receptors in the VTA on GABAergic neurones to reduce GABA release. This disinhibits dopamine neurones in the VTA so increases firing and leads to an increase in DA release in the Nacc.

Question 5

How do stimulants like cocaine and amphetamine work?

Answer 5

Cocaine inhibits dopamine reuptake by blocking the dopamine transporter

Amphetamine is actively taken up into nerve terminals of DA neurones and replaces dopamine in vesicles. This forces the dopamine out of the vesicles, into the nerve terminals and increases synaptic DA concentration

Question 6

How does ethanol work?

Answer 6

It acts directly on dopamine neurones in the VTA.
It inhibits the opening of potassium channels. This prevents after hyper polarisation so DA neurones can increase their firing rate and release more dopamine

Question 7

How does nicotine work?

Answer 7

Nicotine acts on nicotinic acetylcholine receptors on DA neurones in the VTA which leads to an increased firing rate of DA neurones and increases DA release in the NAcc

Question 8

How does Cannabis work?

Answer 8

Cannabis acts on THC receptors on GABA neurones in the VTA. This inhibits GABA IPSPs resulting in decreased GABA release and increased firing of DA neurones

Question 9

Physical withdrawal is ___ important in sustaining drug seeking behaviour than psychological withdrawal.

Answer 9

Less

Question 10

What is negative reinforcement?

Answer 10

• Alleviation of the underlying issue

e. g. take the drug due to its clinical benefit - e.g. relieves symptoms

Question 11

What is positive reinforcement?

Answer 11

Postive reinforcement plays a large role in psychological dependence which can lead to addiction.

You want to take the drug as it makes you feel euphoric rather than taking it to get rid of symptoms (e.g negative reinforcement)

Psychological dependence correlates with relapse and the cravings can persist even after being abstinent for a long period of time

Question 12

What are the 3 major stimuli for relapse in humans?

Answer 12

1) Cues associated with the drug
2) Priming dose (take small amount of drug)
3) Stress

Question 13

The propensity to relapse is LONG term and RAPID:
The study by _____ in 1993 showed that the average time to initial dependence took ___ and then after a period of _____ in _____, the time to develop dependence after the first drink after being ____ took a matter of ___.

What does this show?

Answer 13

Besançon F in 1993
Years
Abstinence in months 
Abstinent 
Days! 

Shows that a small ‘priming dose’ of the substance can turn a previous addict from abstinent to a compulsive user very rapidly - a stimuli for relapse

Question 14

Talk through two methods of assessing rewarding effects of drugs:

What can they methods also be used to study?

Answer 14

1) Self administration
- Intracerebroventricular injections of substances are connected to a lever that the rats can press
- Pressing the level administers the substance
- Rats administer all drugs of abuse that increase dopamine in the NAcc
- They also release allosteric GABA agonists e.g. benzos and although this doesn’t release dopamine in the NAcc it is thought that this is due to negative reinforcement as the drugs relieves the symptoms of anxiety!
- Rats dont administer hallucinogens e.g. LSD - it doesn’t increase activity of DA in the NAcc

2) Conditioned place preference
- Associative memory and conditioned responses are involved here - Pavlovian type approach!
- Inject animal with saline/drug and place in one compartment after saline and other with drug
- Associates one environment with drug of abuse and other with saline
- On test day, animal receives no injection, separating door is removed and animal can move through the whole box
- ‘Drug seeking behaviour’ is exhibited whit drugs that release DA in the NAcc e.g morphine as the animals spend more time in the environment that they associate with the drug as they ‘hope’ to get the drug by being in the environment
- Avoided environments associated with K opioid receptor agonist as dysphoric

Reinstatement - animal version of relapse

Question 15

What does reinstatement assess?

Answer 15

The resumption of previously extinguished drug reinforced behaviour in response to priming doses, cues or stressful situations.

Question 16

How is reinstatement of drug taking measured?

3 Steps in animal models

Answer 16

1) Must initiate self administration behaviour to an adequate level e.g. by using the intracerrebrovascular injections of euphoric substances via levers in rats
2) This must then be followed by a drug free period (extinction phase) - this phase is NOT forgetting about the drug otherwise reinstatement wouldn’t work as it the rat forgot the role of the lever, it would never press it to administer the drug again!
3) The response of the rat to a specific trigger is tested to see if resumption of the behaviour occurs. E.g due to stress, giving priming dose or cue