Lecture 5: Drug addiction

Question 1

How many people used illicit substances at least once in 2015?

Answer 1

250 million

Question 2

How many users suffer from drug use disorders?

Answer 2

29.5 million

Question 3

Positive reinforcement

Answer 3

=in a situation, a behaviour followed by appetitive stimulus

• behaviour will become more frequent in that situation
• will be encouraged more

Question 4

Effectiveness of reinforcement

Answer 4

-greatest if occurs immediately after a response

eg users prefer heroin to morphine as it has more rapid effects, not because it has a different effect

Question 5

Neural mechanisms: what do natural reinforcers cause

Answer 5

=the release of DA in the nucleus accumbent

*aversive stimuli can also trigger the release of DA

Question 6

What do addictive drugs trigger?

Answer 6

• the release of DA in the NAC

* release of DA appears to be necessary but not sufficient for positive reinforcement to take place

Question 7

Where does addiction start?

Answer 7

• In the mesolimbic DA system

- then produces long-term changes in other brain regions that receive input from these neurons

Question 8

Steps of neural mechanisms

Answer 8

1) changes in VTA : A single administration of a variety of addictive drugs increased the strength of excitatory synapses on DA neurons in the VTA.
* VTA= nucleus containing cells that produce dopamine
2) Caused by insertion of additional AMPA receptors into the postsynaptic membrane of DA neurons. This process, normally mediated by glutamatergic NMDA receptors, is the neural basis of many forms of learning.
3) changes in VTA= increased activation in other regions that receive dopaminergic input

 Synaptic changes that cause the compulsive behaviours that characterise addiction only occur after continued use of an addictive drug.
 The most important of these changes appear to occur in the dorsal striatum. The basal ganglia (part of the dorsal striatum) play a critical role in instrumental conditioning, and the process of addiction involves this.

Question 9

Tolerance

Answer 9

=a decrease in sensitivity to the effects of the drug following chronic exposure. Requires an increase in dose to produce the desired effect

Cross tolerance=exposure to one drug can produce tolerance to others

Question 10

Withdrawal

Answer 10

A consistent set of symptoms that appear after discontinuing the use of the drug (often opposite to the initial effect

Question 11

Negative reinforcement

Answer 11

• reduction in withdrawal effects may play a role in maintaining the individuals drug addiction
• The unpleasant effect of withdrawal is also a strong incentive to continue taking the drug. Some people keep taking drugs to avoid the withdrawal symptoms(=aversive stimuli)
• May also explain acquisition of drug taking in certain situations. If a stressed/ unhappy/anxious person takes a drug that eliminates these unpleasant feelings then the drug taking behaviour is likely to be reinforced-negative reinforcement also important early on in drug addiction

Question 12

Craving

Answer 12

=an intense pathological desire for a drug

• can occur long time after quitting
• Taking drugs over an extended period of time produces long-lasting changes in the brain that increase a persons likelihood of relapsing.

Question 13

**Animal models

Answer 13

**

Question 14

Adolescent vulnerability

Answer 14

-pre frontal cortex involved in planning, evaluation of consequences, inhibition of inappropriate responses

 Addicts
 Medial prefrontal cortex (mPFC) is hypoactive in addicts
 Activation of mPFC is inversely related to abusers normal weekly amount of cocaine
 Adolescents more vulnerable to drug addiction than adults
 A time of maturational change of PFC, so more likely to display impulsive, risky behaviour including experimentation with drugs.

Question 15

Cocaine: effects and withdrawal

Answer 15

 Acute Effects:
 Euphoria, arousal, powerful burst of energy, increased sense of well being & confidence.
 Chronic Effects :
 Restlessness, irritability, insomnia, paranoia, anxiety, hallucinations (‘cocaine bugs’). Causes them to scratch at their skin
 Withdrawal:
 depression, cocaine craving, prolonged periods of sleep, bouts of ravenous food intake, anxiety, boredom, lack of motivation, reduced ability to experience pleasure

Question 16

Cocaine: how it works

Answer 16

 Inhibits the reuptake of DA, NA(noradrenaline) & 5-HT (serotonin)
 The reinforcing properties of cocaine are believed to be due to its DA reuptake inhibiting properties
 Dopamine receptor antagonists administered to the NAC reduce cocaine’s reinforcing effects (McGregor and Roberts, 1993)
 Destruction of dopaminergic terminals in the NAC interferes with cocaine’s reinforcing effects (Caine & Koob, 1994)

Question 17

Amphetamine effects

Answer 17

 Increased alertness and arousal (stimulation of NA neurons arising in the LC)
 euphoria (stimulation of the mesolimbic DA pathway),
 increased sense of well being (less intense than cocaine but longer lasting).
 Chronic Effects :
 Hallucinations
 compulsive and repetitive behaviours that are fixated upon ordinarily trivial aspects of life e.g. at night counting corn flakes in a box, grind teeth (higher doses would activate the nigrostriatal DA pathway)
 ‘paranoid psychosis’ (resemble the symptoms of paranoid schizophrenia)

Question 18

Amphetamine: how it works

Answer 18

 Amphetamine has a similar molecular structure to dopamine and noradrenaline
 It increases the level of DA, NA & 5-HT in the synaptic cleft
 increases release (by increasing both spontaneous leakage from neurons & stimulated release)
 inhibits reuptake back into the terminals (weaker effect than cocaine)
 mild & temporary inhibitory action on the enzyme MAO (so inhibits normal metabolism of monoamines)

Question 19

Heroine acute effects

Answer 19

 Heroin acts on endogenous opiate receptors in different areas of the brain
 Analgesia (periacqueductal gray matter)
 Hypothermia (preoptic area)
 Sedation (mesencephalic reticular formation)
 Reinforcement (ventral tegmental area & nucleus accumbens)

Question 20

Reinforcement

Answer 20

 Animals will Self Administer (SA) morphine/ heroin IV
 opioid receptor antagonists into VTA or NAC decrease heroin SA (review Di Chiara & North 1992)
 Dopamine
 opiates increase DA release in NAC (Pontieri et al 1995)
 DA lesions or D1 or D2 receptor antagonists impair opiate reward

Question 21

Treatments: Agonist therapy

Answer 21

 Methadone for heroin addiction
 Liquid form: slower route of administration than injection so does not produce the same high as a heroin injection
 Long half-life: long-lasting, so receptors remain occupied for a long time, which means an injection of heroin has little effect.
 Nicotine patches/ gum/ e-cigs for nicotine addiction

Question 22

Treatments: partial agonist therapy

Answer 22

 Buprenorphine for opiate addiction
 Partial agonist for m opiate receptor (high affinity for the receptor but activates it less than the normal ligand).
 Blocks the effects of opiates and itself produces only a weak opiate effect

Question 23

Antagonist therapy

Answer 23

 Naltrexone for heroin addiction
 Naloxone plus buprenorpine ensures the combination has no abuse potential
 Immunisation (cocaine addiction)
 Conjugate the drug to a foreign protein in order to stimulate the bodies immune systems, thus developing antibodies to the drug and preventing the drug from crossing the blood brain barrier.
 Promising results from animal and human trials