REWARD SYSTEMS OF THE BRAIN?. ICSS and brain reward centers? “A series of misinterpretations.” The lateral hypothalamus (LH)/ The reward center?

REWARD SYSTEMS OF THE BRAIN?

ICSS and brain reward centers? “A series of misinterpretations.”

The lateral hypothalamus (LH)/

The reward center?

Animal Models of reward• James Olds and Intra-cranial Self-stimulation…Intial studies of learning and

RAS stimulation..serendipity!

• Place preference• 2 lever choice

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

The Ventral tegmental Area (VTA) Dopaminergic pathways

VTA

A component of MFB axons arise from the VTA-DA projection paths.

mesolimbic and Mesocortical Dopaminergic pathways

The VTA projects to the nucleus accumbens and to the medial prefrontal cortex

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)

Microdialysis Studies support the role of DA in Reward

Microdialysis probe

Microdialysis probe: an ultra small cellular fluid collection system

When Implanted in targeted brain regions

“Extracellular fluids “ can be collected and analyzed for neurochemical content. Different chemicals produced different “Chemical signatures”…including DA.

ICCS increases DA release in Nucleus Accumbens

Drugs increase DA release in accumbens

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.

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).

But was this pleasure?

• Perhaps not.

• B19’s 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.

•

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

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

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.

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).

The Incentive-Sensitization theory and Implicit perceptions?

• The incentive–sensitization 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.

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.

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).

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.

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)

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.