Reward and addiction

Question 1

What were the findings of the experiment by Olds and Milner (1954)?

Answer 1

• Observed that a single animal appeared to “enjoy” brain stimulation
• “By the time the 3rd electrical stimulus had been applied the animal seemed indubitably to be coming back for more”
• Subsequently showed that animals would press a lever repeatedly in order to receive electrical stimulation of specific brain areas
• – Effect was region specific
• – Dependent on stimulus strength
• – This is self-stimulation
• – Very powerful motivator
• Best brain areas for electrical stimulation = median forebrain bundle, ventral tegmental area
• – Also (but less effective): prefrontal cortex, nucleus accumbens
• The effects of stimulation current on press rate:
• – Not supported below a certain current (threshold)
• – As the current increases the press rate increases
• Effects of drugs/lesions on press rate:
• – Threshold current is increased by dopamine antagonists
• – Press rate is decreased by low doses of dopamine antagonists
• – Pressing abolished by lesions of median forebrain bundle
• Self-stimulation causes an increase in dopamine release in nucleus accumbens

Question 2

What happens to the self-administration of cocaine or amphetamine in animals if a dopamine antagonist is given?

Answer 2

• Press rate increases in order to receive more drug to overcome the effect of the antagonist
• As long as small dose of dopamine antagonist
• – If too large, will cause an extinction effect

Question 3

What evidence is there for the role of dopamine in drug use?

Answer 3

DiChiara and Imperato, 1988:
- Shows that the drugs (amphetamine, cocaine, nicotine, morphine and ethanol) that can be abused by humans increase synaptic dopamine concentrations in the nucleus accumbens of rats
- Larger responses in the nucleus accumbens then the striatum
Berridge and Robinson, 1998
- Dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning
- Rats were depleted of dopamine in the nucleus accumbent and neostriatum by up to 99% using 6-hydroxydopamine
— Researchers applied the ‘taste reactivity’ measure of affective reactions to assess the capacity of dopamine-depleted rats for normal affect (hedonic and aversive reactions), modulation of hedonic affect by associative learning (taste aversion conditioning) and hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration)
— Found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability
- Conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning
— Instead it may be more important to incentive salience attributions to the neural representations of reward-related stimuli (a distinct component of motivation and reward)
Barbano and Cador, 2006
- Dopamine plays a motivational role whereas opioids (Pecina and Berridge, 2005), endocannabinoids (Pecina, Smith and Berridge, 2006) and the GABA-benzodiazepine neurotransmitter system (Jarrett, Limebeer and Parker, 2005) mediate the hedonic component

Question 4

What evidence is there that dopamine release in the nucleus accumbens signals reward?

Answer 4

• Self-stimulation and effects of dopaminergic drugs
• Drug self-administration (systemic and local)
• Conditioned place preference
• Dopamine release in nucleus accumbens during rewarded behaviour
• Drugs which enhance these behaviours, evoke dopamine release in nucleus accumbens when given alone
  — Many of these drugs have addictive potential in humans
  — Hence there is believed to be a link between dopamine release in nucleus accumbens, reward and addiction
  — Many behaviours and/or stimuli associated with drug taking become reinforced
  • Promote drug taking
  • Induce craving for drugs
  • Induce physical symptoms similar to withdrawal symptoms
  • Implies a link with conditioning
  • These behaviours may activate dopamine systems
  • Behaviours associated with reward (actual or potential) may also become addictive (e.g. gambling, exercise, eating disorders)
• But aversive stimuli also evoke dopamine release in nucleus accumbens so dopamine release in nucleus accumbens signals more than just reward – perhaps salience?

Question 5

What is conditioned place preference?

Answer 5

Prus, James and Rosecrans (2009)

• A standard preclinical behavioural model used to study the rewarding and aversive effects of drugs
• Training: the animal (typically a rat or mouse) is placed in the central chamber of a 3 chamber cage
• – R = rewarded chamber
• – C = control chamber
• Test: the rat is again placed in the central chamber, but there is no reward present
• – Measure percentage of time spent in conditioned reward chamber
• If you give a dopamine antagonist (such as haloperidol), the rat spends equal time in both chambers (no induction of conditioned place preference, Weeks and Collins, 1987)
• If amphetamine is given, the rat spends more time in the conditioned reward chamber (leading to a conditioned place preference, Trazon et al., 1992)