neurobiology 2

Question 1

Four key points of Robinson and Berridges Incentive sensitization model

Answer 1

• Addictive drugs share the ability to produce long-lasting neuroadaptations in particular parts of the brain
• The parts of the brain sensitive to change are those involved in incentive motivation and reward
• Critical adaptations involve hypersensitization of brain reward pathways to drugs and drug cues
• The sensitized systems do not mediate the hedonic effects of drugs (e.g. liking), but instead mediate brain systems involved in incentive salience and motivation (e.g. wanting)

Question 2

Briefly describe the incentive sensitization model

Answer 2

Through associative links between drug effects and cues, the brain, specifically the nucleas accumbens shell, attributes incentive value to drug-related stimuli. Such stimuli elicit the conditioned behaviour- drug taking, hence cravings to take drugs are experienced. Incentive value refers to expected reward incentives offered by the stimuli. For example, drug related stimuli is made salient as it is associated with euphoria. Incentive salience of drug related stimuli occurs due to sensitization of the nucleas accumbens reward circuitry.
The long-lasting nature of the adaptations leaves addicted users sensitive to relapse, even after relatively long periods of abstinence. Incentive salience is produced by principles of Pavlovian conditioning, i.e. stimulus-response contingencies. This is therefore dissociable from explicit desire.

Question 3

Neural mechanisms of sensitization to salient incentive stimuli

Answer 3

• In the addicted individual, a drug dose is given, resulting in increased dopaminergic release in the nucleus accumbens which also results in glutamate release in Nacc.
• Release of glutamate is linked to GABA which either inhibits or increases the effect of dopamine
• Drug use primes and sensitises the dopaminergic rewards pathway in a chronic ad intense way.
• External events are also linked to this i.e. being with the set of friends in which you take drugs with, being in a certain setting etc
• This then results in hyper-sensitivity of receptors in NAcc to drug related stimuli and events.
• Person thus goes from experiencing the biological effects (niceness of being high, whether reward pathway has enough dopamine receptors available or not), to the psychological (cues that make person think they’ll be getting the drug).
• This leads to cravings and eventually a loss of control where a cycle of addiction ensues
o Drug use primes and sensitises reward pathway
o Tuned in to related cues about availability of drugs
o Craving
o Seek/use drugs

Question 4

Evidence for incentive sensitization theory

Answer 4

Hobbs et al 2005 conducted an experiment to investigate whether wanting and liking of alcohol were dissociable in humans. Self-reported liking of alcohol and wanting of alcohol (indexed by weekly alcohol consumption) were measured. It was found that the two were not associated.

Question 5

Evidence for neural mechanisms of incentive sensitization theory- 2 studies

Answer 5

 Volkow et al 2006 conducted a PET study investigating the responses of cocaine addicted subjects to drug related stimuli. Participants watched either videos of nature scenes or videos of someone smoking cocaine. Results showed that participants showed significantly more dopamine release into the caudate putamen (in the dorsal striatum) in response to the cocaine video compared to the video of nature scenes, and that dopamine response was significantly correlated with self-reported craving. Shows that drug craving is a conditioned response to dopamine reward, which in turn is more sensitive to drug stimuli than neutral stimuli.
 Volkow et al 2008 further investigated whether drug craving is a conditioned response to dopamine reward in general or only in the context of drug related stimuli.
 Volkow et al 2008 conducted a similar study using cocaine addicted subjects who were given oral methylphenidate (20 mg), which significantly increases dopamine in striatum. Some participants were shown a video of people using cocaine and others were not. Self-reported cravings and levels of dopamine in the striatum were then measured. Results showed that cravings were only associated with increased dopamine in the striatum when the methylphenidate was coupled with the cocaine video. Highlights the context dependency of dopamine reward in eliciting the conditioned response of drug cravings.