Transcript Drug Addiction and Reward

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 Selfstimulation…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
A component of MFB axons arise from the VTA-DA
projection paths.
VTA
mesolimbic and Mesocortical
Dopaminergic pathways
The VTA projects to the nucleus accumbens and to the
medial prefrontal cortex
DA agonist and antagonist effects
on 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 Incentive-Sensitization Theory
'wanting' is not 'liking'
• The neural system are proposed to be separate .. (Robinson and Berridge)
Then what is the role of mesocortical, 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.