Theories of Addiction III Flashcards
Incentive sensitization view
- exposure to drugs changes the brain - it adapts
- the systems that are adapting are the ones involved in incentive motivation and reward
- repeated exposure sensitizes reward systems to drugs and drug associated cues
- separate reward into liking and wanting. shown that changing DA transmission and there is strong effect on wanting, no effect on liking. sensitized brain systems mediate wanting (incentive salience).
DA role in reward
suggested there’s a basic pleasure/liking response across all species. baseline pleasure response that is not learned - activate/block DA system but doesnt effect liking response. but blocking opiate system, lose this response (opiate system important for pleasure) - opiates can double liking response. DA mediates wanting. can block wanting without effecting liking. EXPERIMENT: feed subjects a diet full of APTD (acute phenylalanine tyrosine depletion). without phenylalanine=no tyrosine=no DA. end result, subjects have lower DA since theyre missing precursors. exposed subjects to different doses of cocaine. report how euphoric(pleasure) and how much they want the drug after experiencing it. with increased doses, report higher euphoric effects (no difference between groups). increased doses report higher wanting but APTD subjects show lower wanting at certain dose. manipulate DA results in blocking wanting but not pleasure. Wanting increases over repeated exposure because DA system sensitizes.
- most important physiological change that is induced by repeated drug exposure is hypersensitivity to the incentive motivational effects of drugs and drug associated cues. incentive sensitization causes an attentional bias because those cues are becoming so salient - drives pathological motivation.
supporting evidence for incentive sensitization view (4)
- in animals, cocaine sensitization increases conditioned reinforcing effects of cocaine associated stimuli
- in humans, repeated exposure to amphetamine showed that there is sensitization of the behaviour and DA release in the striatum even a year after last drug treatment.
- in addicts, there is attentional bias towards drug-related cues. EXPERIMENT: subtle changes involving items related to alcohol, cannabis, not related to either. measured time it took to identify change. decreased time if theyre alcohol users and change was alcohol related. same for cannabis users. identified change more quickly due to incentive salience. heavy users faster than light users.
- in cocaine dependent subjects, repeated exposure results in stronger craving (increased wanting) compared to controls, but lower high (pleasure). liked it less but want it more.
critique of incentive sensitization view
animals need to experience reward at least once under DA deficient conditions in order to show decreased motivation. EXPERIMENT: animals run to end of box for heroin injection. need to experience running with antagonist and then running post antagonist is slower demonstrating decreased motivation - rewarding feeling isnt there so they run much slower.
modulation of behavioural sensitization by environmental stimuli
show that environmental novelty can enhance the development of sensitization of the psychomotor effects of psychostimulants. EXPERIMENT showing development of behavioural sensitization: 4 groups of rates (saline/amphetamine, home/novel). administered amphetamine IV (no clear cue to indicate drug receiving). at different times, rats received infusions for 7 days. novel rats transported to a test chamber to get drug. after 7 days of treatment free, rats injected with a single acute dose of amphetamine. not much locomotor change in home environment rats. Even before challenge novel rats showing increase locomotor activity just by being in novel environment. after challenge, increased locomotor activity in novel group, home don’t show sensitization.
- in novel environment, there are many novel cues so its easier to make stronger association with effects of the drug - helps development of sensitization. stress from moving environment to environment might also sensitize response to psychostimulants (cross-sensitization). can look for changes in expression of immediately early gene (IEG) from novel and home. active neurons have increased IEG. novel amphetamine group have increased IEG expression. there are novelty specific cocaine induced adaptations that increase spine density in NAc.
deficits in executive function model
decision making results from interaction between 2 competing systems: impulse and reflective. IMPULSE system has a major role in linking stimuli to the emotional affective properties that the stimuli are carrying. contains amygdala and amygdala striatum pathway. amygdala striatum important in assigning values to cues associated with a particular stimulus. damage to the amygdala results in showing no emotional response. repeated exposure lead drugs to gain strong affective properties by activating amygdala striatum pathway. this pathway is overactive in addicts. REFLECTIVE system represents this concept where we learn about our environment and experiences. when exposed to stimuli, some kind of affective memory is created. doesnt have to be personal experience (knowledge from learning). proper decision making considers these memories. problem with this process leads to ignoring warning memories. VMPC critical for function of this system, critical for process of affective memory system that feeds downstream to block inappropriate behaviours when needed.
Phineas Gage
demonstration of deficient decision making - example of what happens when VMPC is damaged. can identify damage in similar areas in addicts. Assess risk aversion/seeking using Iowa Gambling test = 67% of addicts show performance similar to VMPC patients (risk seeking) but so do 27% of normal people. other deficits include overactive impulse system, cannot filter irrelevant information.
Bechara’s view = poor decision making leads to addiction.
reduced reward sensitivity and PFC disfunction
DA critical for reward and development of addiction. EXPERIMENT: expose people to ritalin (MPH), causes the release of DA, use radioactive raclopride and PET scans. lower signal means increase DA receptors occupied by DA. correlates very well with self reported highs. but, repeated exposure downregulates DA receptors and DA release. there is reduced density of D2 receptors in the striatum, DA release is decreased in chronic alcohol users following IV MPH. repeated exposure to drugs and overstimulation of DA pathway create powerfully learned associations. cues associated with drug use can strongly drive activation of DA pathway. PET scan shows effects of cocaine on brain. signal is much lower meaning a lot of DA released by those cues. changes in DA system also associated with reduced activity in OFC. PET scan using radioactive glucose - if you label glucose can estimate how much glucose neurons use, how active they are. reduction in metabolism in OFC - reduction strongly correlated with reduced density of D2 receptors in striatum. The iRISA syndrome = impaired response inhibition and salience response. under normal circumstances, stops behaviour that is inappropriate. in an addicted state, there’s a very strong drive in amygdala-striatum pathway, a deficit of input from PFC leading to GO behaviour not being controlled, cannot stop inappropriate behaviour.
deficit in executive function demonstration
trained animals to seek and take cocaine. once self administration behaviour was achieved, animals exposed to shock. there is a risk now - shock - in seeking cocaine. some rats showed resistance to shock. once they identified rats as resistant or sensitive, they looked at their brain and recorded from mPFC. identified that they needed higher drive to excite neurons in resistance rates - neurons were less excitable in mPFC. naive rats fire at normal rate. sensitive rate fire less (exposure to cocaine changes firing). resistant rates dont fire after 1 or 2 action potentials. just the exposure to cocaine changes firing rate but that change is stronger on the resistant rats. used optogenetics to see if they could change the resistant rats to make them sensitive. drive them artificially to make the neurons fire in resistant rats. introduced channelrhodopsin into mPFC. just infusing virus did not change anything. in the punishment phase, they activated the neurons with blue lights while the punishment occurs. when the light is activated, they seek less cocaine, becoming sensitive to the punishment. also showed the opposite (make sensitive rats resistant). infused them with halorhodopsin in PFC to make them resistant. virus itself did not change anything. in the punishment phase, yellow light is activated, suddenly they take more drug regardless of the punishment. hesitation to press lever is reduced - becoming resistant to punishment.
