Reward, Motivation and Addiction

1
Reward, Motivation and Addiction
motivation covers things from thirst and hunger
to agression and mating it does not have to be
immediate- foraging for food is a process reward
refers to reinforcing a positive outcome ie.
pleasure or fulfilled appetite "an animal's
degree of motivation can be assessed by its
capacity to work toward a goal" positive
reinforcement provides a reward for a
behavior negative reinforcement promises an
adverse stimulus if an action occurs punishment
is the adverse stimulus
2
Reward, Motivation and Addiction
hypothalamus is considered important for
motivation based on its hormonal regulation of
behaviors such as hunger, mating, and
thirst less basic urges and motivations,
however, are affected by the amygdala
preparative activities (ie. sexual displays,
learned 'pleasures', etc) dopamine (from the
substantia nigra) appears important for causing
behaviors associated with feeding and
locomotion blocking dopamine using 6-OHDA
mimics some motivational deficits dopamine
appears to be an initiator of actions based
on lesion and receptor blocade experiments
3
Reward, Motivation and Addiction
dopamine drives the initiation of a number of
different trained and native responses--
activation centers may be normal, but the
initiation is not, so animals have
'behavioral deficits' motivation reinforcement
can be accomplished by direct stimulation, but
artificial stimulation in humans was difficult to
interpret animals which learned a behavior
for a reward (water) learned better with
amphetamine facilitating learning even though
it usually supresses thirst dopamine lesions
in the nucleus accumbens blocked the motivation
4
Reward, Motivation and Addiction
amygdala lesions block learning that actions
would lead to rewards nothing is wrong with the
behaviors themselves, but associating certain
actions with generating desired outcomes is
missing or reduced amygdala projects to the
ventral striatum and links emotion to
behaviors glutamatergic amgdala projections
dopaminergic projections to ventral striatum
regulate GABAergic output to the globus
palladus ventral striatum has been linked to
driving drug seeking and drug taking behaviors
5
Reward, Motivation and Addiction
drug addiction is a repetitive, chronic disorder
characterized by 1) compulsion to seek out
and take the drug 2) inability to limit
intake 3) negative emotional state when drug
is not available includes both illegal (ie.
heroin, cocaine) and legal (alcohol,
nicotine) occasional use of an addictive drug
is separate from addiction- the behavioral and
biological differences between the 2 are being
studied addictions can be of 2 overlapping
types 1) impulse control disorders, where
pleasure is followed by guilt 2) compulsive
disorders where anxiety is followed by
relief
6
Reward, Motivation and Addiction
3 stages of addiction moving from impulsive
tocompulsive behavior 1) binge/intoxication
2) withdrawal/negative effect 3)
preoccupation/anticipation medial forebrain
mediates both natural and artificial rewards
includes ventral tegmentum, nucleus accumbens,
amygdala and cortex has domaminergic inputs as
a vital part (with serotonin, GABA,
etc) psychomotor stimulants work on the
mesolimbic dopamine systems ie. medial system
above includes addictive drugs (ie. cocaine)
these types of drugs increase
neurotransmitters at synapses dopamine
antagonists in nucleus accumbens and
amygdala stop self- administration
7
Reward, Motivation and Addiction
stimulants and opiates can sensitize dopamine
systems to amphetamines may be mediated by
dopamine autoreceptors, NMDARs, or adrenal
hypothalamic stress hormones natural opiate
peptides are present m-opioid receptors mediate
most heroin/morphine addiction and
effects- antagonists block effects opioids do
NOT depend on dopamine but affect other areas
in pathway nicotine stimulates nAChR which
potentiate dopamine systems
m opiate receptor activation
8
Reward, Motivation and Addiction
alcohol, barbituates, and benzodiazapines are
anti-anxiolytics with sedative/disinhibition
properties GABAergic neurons in the amygdala
mediate many anti-anxiety actions GABAergic
inhibitors block alcohol reinforcement same
region most affected by m-opioids alcohol may
also inhibit glutamate and serotinergic
neurons
9
Reward, Motivation and Addiction
positive feelings from drugs eventually change to
compulsive behavior corellates with the switch
from drug use to drug dependence this switch
often accompanies desensitization of the normal
receptors forcing more use of the drug, or
craving prolonged lack of use leads to
withdrawal usually opposite symptoms of the
drug many drugs have physiological as well as
behavioral effects during withdrawal medial
dopamine system is usually misregulated during
withdrawal amygdala is also linked to avoidance
behaviors
10
Reward, Motivation and Addiction
effects of many addictive drugs can be described
as a 2-phase process a-process is the positive
desired effects occurs first, decays quickly
b-processes is the negative or adverse effects
second, decays slowly as addiction grows,
a-process benefits decrease while b-process is
more negative monoamines (dopamine and
serotonin) are both linked to drug
reinforcement corticotropin releasing hormone is
up- regulated during withdrawal (ie.
stress) stresss can also cause more drug use to
try and relieve the stress
11
Reward, Motivation and Addiction
drug relapses can be caused by stress, or by
other conditions which cause similar effects
to drug administration similarity of neuronal
action may trigger relapses same brain regions
(ie. amygdala, nucleus accumbens) involved in
dependence, withdrawal, and relapse CREB,
FosB, and other leucine-zipper transcription
factors regulate long term changes in drug
addiction