REWARD SYSTEMS OF THE BRAIN?

1
REWARD SYSTEMS OF THE BRAIN?
2
ICSS and brain reward centers? A series of
misinterpretations.

• The lateral hypothalamus (LH)/
• The reward center?

3
Animal Models of reward

• James Olds and Intra-cranial Self-stimulationInti
  al studies of learning and RAS stimulation..serend
  ipity!
• Place preference
• 2 lever choice

4
BUT! The medial Forebrain Bundle (MFB) runs
through the LH
The MFB is a large tract that arises from many
different nuclei and projects to many forebrain
regions
5
The Ventral tegmental Area (VTA) Dopaminergic
pathways
A component of MFB axons arise from the VTA-DA
projection paths.
VTA
6
mesolimbic and Mesocortical Dopaminergic pathways
The VTA projects to the nucleus accumbens and to
the medial prefrontal cortex
7
DA agonist and antagonist effectson ICSS

• DA Antagonist (drugs that block the effects of
  DA ) reduce ICSS potency ( actually increase
  rates of responding suggesting the reward value
  has diminished)
• DA Agonist (drugs that enhance the effects of
  DA ) Increase ICSS potency ( actually decrease
  rates of responding suggesting the reward value
  has increased)

8
Microdialysis Studies support the role of DA in
Reward
Microdialysis probe
9
Microdialysis probe an ultra small cellular
fluid collection system
10
When Implanted in targeted brain regions
11
Extracellular fluids can be collected and
analyzed for neurochemical content. Different
chemicals produced different Chemical
signaturesincluding DA.
12
ICCS increases DA release in Nucleus Accumbens
13
Drugs increase DA release in accumbens
14
Brain reward and Humans

• Functional brain imagery of brain activity after
  administration of a learned reward in humans has
  found changes in brain activity in the nucleus
  accumbens, medial orbitofrontal cortex and
  anterior cingulate cortex.

15
What about ICSS in Humans

• In humans, a well-known case was B-19, a young
  man implanted with stimulation electrodes by
  Heath and colleagues in the 1960s.
• B-19 self-stimulated at very high rates and
  would be upset when the stimulation was
  disallowed.
• Appeared to produce feelings of pleasure,
  alertness, and warmth.
• He also reported sexual arousal and described a
  compulsion to masturbate (p. 6, Heath, 1972).

16
But was this pleasure?

• Perhaps not.
• B19s electrode stimulation evoked desire to
  stimulate again and strong sexual arousal while
  never producing sexual orgasm or clear evidence
  of actual pleasure sensation.
• Alternatively The stimulation may not have
  affected reward but may have produced a want
  to do sexual acts.

17
The Incentive-Sensitization Theory 'wanting' is
not 'liking'

• The neural system are proposed to be separate ..
  (Robinson and Berridge)

18
Then what is the role of meso-cortical,
mesolimbic DA systems?

• ..to increase the salience' of stimuli and
  events associated with activation of the system.
• Stimuli are imbued with salience, making them
  attractive, 'wanted', incentive stimuli.

19
The Incentive-Sensitization theory and Drug
Addiction ?

• Drug-induced sensitization of DA pathways cause
  pathological incentive motivation (wanting) for
  drugs (Robinson and Berridge, 2008)
• Dopamine normally functions to trigger reward
  wanting. In drug dependence, drugs alter
  this system.
• Repeated use of such drugs makes the dopamine
  system hyper-responsive to drug cues
• Drug cues become difficult for addicts to
  ignore, and lead to intense wanting (cravings
  and/or relapse).

20
The Incentive-Sensitization theory and Implicit
perceptions?

• The incentivesensitization theory holds that
  drugs can activate wanting in the absence of
  conscious awareness.
• Activation of the DA pathways can sometimes
  produce goal-directed
• behavior (wanting) not only in the absence of
  subjective pleasure, but in the absence of
  conscious awareness of wanting itself.

21
Evidence supporting the Incentive-Sensitization
Theory

• Lesions studies, and studies using selective
  dopamine agonists or antagonists, as well as
  other similar manipulations have no effect on
  rats judgements of hedonic properties of taste
  stimuli1 (for reviews, see Berridge ).
• Many studies show that dopamine and accumbens
  neurons often become most active in anticipation
  of rewards, not during the reward phase
• DA systems are also activated by aversive,
  stimuli and events.
• In humans DA antagonists, such as pimozide or
  haloperidol, do not reduce amphetamine-induced
  pleasure.

22
But What About Pleasure?

• Rewarding/pleasurable stimuli activate Opioid,
  anandamine ( an endogenous cannabis-like
  neurotransmitter) and GABA release in the
  Accumbens.
• Crucial for pleasurable feelings associated with
  delicious foods, sex, drugs, and other rewards (a
  role previously thought to be played mostly by
  brain dopamine systems).

23
Evidence for separate pleasure circuits?

• Enjoyable sweet tastes produce characteristic
  licking responses in rats. Aversive bitter
  tastes produce gaping and head shaking.
• An opioid drug (Damgo) was micro-injected into
  the VTA of rats
• Rats ate much more food and had significantly
  greater number of "liking" expressions when they
  tasted the food.
• "Liking" expressions were defined as positive
  facial lip licking expressions that are similar
  in rats, monkeys, apes and even human infants.

24
PLEASURE/LIKING?

• In this fashion Several brain areas have been
  found to produce changes in Liking
• E.g... activation of opioid circuits in the
  nucleus accumbens (e.g., by microinjecting
  morphine there) causes increased pleasure
  liking.
• Thus the VTA- Accumbens pathway appears important
  in wanting (DA) and Liking (opioids etc)

25
Relation of incentive sensitization to cognitive
dysfunction

• Other brain changes contribute importantly to
  addiction too, including damage or dysfunction in
  cortical mechanisms that underlie cognitive
  choice and decision making (Robinson Berridge
  2000, 2003).
• Many studies have indicated changes in executive
  functions, involving how alternative outcomes
  are evaluated and decisions and choices made,
  occur in addicts and animals given drugs (Jentsch
  Taylor 1999 Rogers Robbins 2001 Bechara et
  al. 2002 Schoenbaum Shaham 2008).
• The impairment of executive control plays an
  important role in making bad choices about drugs,
  especially when combined with the pathological
  incentive motivation for drugs induced by
  incentive sensitization.