Opioids: Reinforcement and Dependence Flashcards
Describe reinforcing effects of opiates
- Animals readily acquire operant self-administration of
opiates - Self-administration increases over time to a
stable/optimal level in blood - Animals readily develop conditioned place preference for
opiate use
Describe mesolimbic dopamine pathway
Opioids function within the mesolimbic
dopamine reward pathway.
Dopaminergic projections from the
ventral tegmental area (VTA) project to
the Nucleus accumbens (NAc) providing
motivational salience to information
passing to the ventral palladium.
In the absence of reinforcing stimuli DA
release is under tonic inhibitory control of
GABA interneurons.
Dopamine release in the NAc provides a
positive reinforcement to associated
behaviours.
Opioids function within the
mesolimbic dopamine reward
pathway.
Endorphin-secreting neurons
provide inhibitory input to
GABAergic interneurons in the
VTA.
Endorphin release or MOR
activation results in disinhibition
of NAc DA release.
What is the role of opiates at GABAergic interneurons?
Opiates act at GABAergic
interneuron terminals (axoaxonal
transmission) to disinhibit NAc
dopamine release and increase
motivational salience.
Describe the role of dynorphin
Dynorphin provides direct inhibitory
control over the mesolimbic DA
neurons.
Dynorphin release or KOR activation
results in inhibition of NAc DA release.
Describe reinforcing effects of opioid receptor agonists
- Agonists at the κ receptor do not
acquire self-administration and will
actually induce conditioned place
aversion - Endogenous opioids provide salience
through mesolimbic DA modulation - Opiates act principally through μ-opioid
receptors to provide incentive salience - Dynorphins act through κ-opioid
receptors to provide aversive salience - Dopamine lesion using 6-OHDA
reduces but does not abolish opiate
self-administration
Describe opioid reinforcement
- Reinforcement increases with different routes of drug administration
- Heroin is more reinforcing than morphine due to more rapid transit across the BBB
- IV administration is more reinforcing than oral or IM administration due to more rapid access to the BBB
- Drugs available by inhalation (esp. nicotine) have very rapid access to the brain and are highly reinforcing
Describe rebound hyperactivity
- As opiates are depressants (in that they depress CNS
function) their withdrawal results in CNS hyperactivity - Withdrawal symptoms can be described as rebound
hyperactivity as neural circuits operate at a disturbed
homeostatic level - Withdrawal effects contrast/oppose acute effects of
intoxication
Describe role of opioids in learning and memory
- NMDA receptor antagonists (MK801,
dizocilpine) reduce tolerance to analgesia as
measured by tail-flick latency
Describe models of addiction
- Gateway hypothesis
*
… - Physical dependence model
- Establishment and maintenance of addictions
manifests from development of dependence - Abstinence (withdrawal) results in craving,
leading to relapse - Posits addiction is a result of negative
feedback in trying to eliminate unpleasantness
of abstinence - Role of classical conditioning in craving and
relapse - Conditioning of withdrawal symptoms
Describe positive reinforcement model
- Drug addiction results from
positive feedback – compulsive
desire to experience drug-related
euphoria
Describe incentive sensitization model
- Increased use occurs with increased wanting even
though drug liking remains the same or decreases
Proposes two distinct underlying neurobiological
processes for liking and wanting
* Drug wanting system undergoes sensitization
* Mesolimbic DA system readily sensitized
* Drug liking system undergoes tolerance
Describe opponent process model
- Adaptive processes lower hedonic set point
such that chronic users experience dysphoria
in the absence of drugs
Describe limits of incentive-sensitization and opponent-
process models
- Both address neural mechanisms of drug abuse
- Both explain different aspects of addiction
- Incentive-sensitization provides an explanation of drug craving
- Opponent-process provides an explanation of dysphoria during
withdrawal
Describe disease models of addiction
- Disinhibition (predisposition to
impulsivity, hyperactivity, antisociality)
is a predictive risk of substance-use
(regardless of the substance)
