Lecture: 11 Addiction

Describe Pavlovian learning paradigms used in researching addiction?

Conditioned place preference is the term used to describe this type of paradigm. In this, rats are placed in a specific and distinct context, which is then associated with a specific type of drug. At test, symbols of this context are placed elsewhere, if the rat approaches these symbols, addiction is recognised.

Describe Instrumental learning paradigms used in researching addiction?

Typically a self-administration paradigm, wherein rats are placed with a lever which when pressed produces the drug. In this case, rats learn that the lever press leads to the outcome and drug association.

Describe why drugs are rewarding?

Drugs are rewarding due to how they interact with the mesolimbic dopamine system. Drugs typically activate this system by reducing reuptake of dopamine neurotransmitters with the brain. The axons of these neurons are very widespread projecting across the VTA and into the prefrontal context, generally causing pleasure signals.

Describe evidence for the activation of the human mesolimbic dopamine system?

Evidence for activation comes in the form of imaging scans of human brains whilst a user is using specific types of drugs.

Describe what the nucleus accumbens?

Is part of the VTA that is also implicated in drug reward systems, evidence for this comes from measurement of dopamine following the administration of cocaine, amphetamine or nicotine, all of which shows an increase in active dopamine.

Describe dopamine neurotransmission in the pre-synaptical neuron ?

Tyrosine is converted into L-DOPA, which is then converted into dopamine, this synthesis occurs and is stored in vesicles in the neuron, when the action potential arrives, this vesicle travels to the membrane and opens to release dopamine.

Describe how dopamine rewards vs. how it is reduced in the synaptic cleft (i.e. doesn’t reward).

Rewarding
Binds to the D1 dopamine receptor on the postsynaptic neuron, this will raise concentrations of cAMP, which is rewarding.
Reduces rewards
Binds to D2 dopamine receptors in the presynaptic neuron, reducing amount of dopamine and therefore reduces cAMP
Removed from the synaptic cleft via a re-uptake pump and dopamine transporter
Inside the presynaptic terminal, monoamine oxidase deactivates dopamine.

How do drugs of abuse increase dopamine

Drugs like cocaine block the reuptake of dopamine, by attaching to D2 receptors and causing more dopamine to interact with and cause increases in the level of cAMP.
Opiates may function differently causing flow on effect rather than interacting directly with the dopamine system.

Explain Olds and Milner's experiment and its implications on why people take drugs.

Olds and Milner experiments involved attaching electrical probes into the medial forebrain bundles of rats, a part of the brain which when stimulated will interact with axons of VTA dopamine neurons. Found that rats will press on the lever causing the stimulation repeatedly over 4,500 times an hour.
This suggests that people take drugs due to the pleasure dopamine provides, people’s brains are ‘hijacked’ by the abuse of drugs.

Describe incentive sensitisation as a theory underlying why people persist in taking drugs.

The mesolimbic dopamine pathway is involved in the attribution of incentive salience in the stimuli associated with its activation. Addictive drugs over long periods of usage causes sensitisation of the pathway, causing incentive value to the act of drug taking and the stimuli that is associated with the drug taking.

Describe the state of the evidence around incentive sensitization as a theory?

Not a lot of evidence, however, key evidence around this theory involves how preexposure to amphetamine causes rats to react to dopamine differently. The longer the pre-exposure the more activated dopamine is.

Describe advantages to the incentive sensitisation theory

Attempts to integrate psychological explanation with dopamine function
Very obvious link to neurobiology
Consistent with the important role accorded craving by addicts
Does not accord drug withdrawal a causal status in addiction and thus could be applied to many drugs

Describe limitation to the incentive sensation theory

Lack of clinical evidence for sensitisation of drug responding among human addicts
Not much evidence for dissociations between wanting and liking in human addicts or in animals based on drugs of abuse

What is the opponent process model?

States that Addiction is the result of compensatory responses that drive drug-withdrawal. The motivation to take drugs shifts across the course of addiction, and although initially we take drugs because they are rewarding, eventually we take drugs to alleviate withdrawal as the B process overcorrects and causes withdrawal.

What is the A process?

Occurs in response to the administration or ingestion of the drug, does not change and it will always produce the same response to the drug. It is the B process that changes over time.

What is the B process?

It produces the opponent physiological effect, the B process is slower to activate and last longer than the A process.

What are the advantages and disadvantages of the opponent process model?

Advantages– Explains many features of addiction– Would meet DSM criterion for diagnosis of substance dependence– Does not accord drugs of abuse any special role– Can be reconciled with neurobiology– May have fundamental importance and relevance to understanding causes of opioid overdose.
Disadvantages– Fails to explain persistent drug-taking in the absence of a withdrawal state (e.g., cannabis, psychostimulants) – Tolerance is not an inevitable consequence of drug exposure

What is Siegel's model of Pavlovian drug addiction?

When people take drugs – the environment becomes a drug associated cue.
– The environmental cue acts as predictive cue that you will take the drug
– This produces activation of the CR (opponent process to drug effect)
– As people increase dose, the environmental cues signal the body should activate the CR
environmental cues cause people to take more drugs over time as CR is assoicated with a compensatory conditioned response.

Explain overdoses in the context of Siegel’s model of Pav Drug Addictions?

– If someone addicted to drugs, takes the drug in a novel environment the CS is not
present and so they do not activate the CR
– Leads to overdose ( commonly seen in injecting room situations)

What does Dickinson & Balleine's account of withdrawal say?

Introduces the instrumental incentive learning account, stating that we learn about the relevance of a reward to our current motivation state in order to seek that reward.
States that a Withdrawal state → acts as a motivational state and enhances the incentive value of the drug as it can alleviate the withdrawal state
That is, the behaviour of repeated administration only occurs after learning, and it does not just automatically occur after initial administration.

Which theories predict increased drug-taking during withdrawal?

Dickinson & Balleine's account of withdrawal
the opponent process model

What do antagonist-based treatments do?

Antagonist-based pharmacotherapies aim to blunt the rewarding effects of drugs.

What are the drugs used in the treatment of alcoholism?

Naltrexone - a competitive antagonist - opioid receptor antagonist A
Acamprosate - a partial GABA agonist and glutamate NMDA antagonist
Disulfiram - increases sensitivity to alcohol to cause an array of aversive symptoms to (hopefully) extinguish learning → DOES NOT WORK

What are the drugs used in the treatment of opioid dependence?

methadone - an opioid agonist with high oral bioavailability and long half-life,
Buprenorphine - parietal opioids agonist
Natrexone - opioid receptor antagonist

What is the number needed to treat to prevent return to drinking for Acomprosate?

12

What is the number needed to treat to prevent return to drinking for Naloxone?

20

Does cue exposure work for treating addiction?

No!

Does contingency management work?

YES! → social rewards may also be used in addition to vouchers

Are treatments to addiction getting better?

Yes