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Suzanne Erb

PSYC62: LECTURE 4: Neurobiology of reward th Have to send group membership by next Friday, Feb 8 , 2013  Drugs of abuse are rewarding initially and liked by the individual  What is reward? o Something that produces a pleasurable experience o Decreases an unpleasant experience would be rewarding o Something that has a positive emotional valence associated with it o Serves as an incentive o Approach behavior o When a behavior leads to a rewarding consequence, that behavior will be repeated in the future  Consequence strengthens the likelihood of the behavior repeating (positive reinforcement)  Negative reinforcement – take away something that is unpleasant o Pavlovian conditioning – pairing something neutral with an unconditionally rewarding experience produces a conditioned response o People seek stimuli associated with primary rewards o No more powerful of a reward than drugs of abuse Neurobiology of brain reward  Natural rewards o Allow an organism to feel pleasure when engaging in behaviors that allow them to procreate o Naturally evolutionarily adaptive role  Artificial rewards o Not adaptive o Play on same effects of natural rewards Olds and Milner  Identified what regions of rat brain are capable of maintaining brain stimulation of reward  In which situations would the rat press a lever to get stimulation  Concluded that specific regions in which rats kept pushing lever for stimulation are part of the reward pathway Brain Stimulation Reward  Different electrodes placed in different regions and figured out which regions rats maintained self-stimulation Reward sites  VTA and its dopaminergic projections to nucleus accumbens and frontal cortex are the primary reward pathway which are all a part of the medial forebrain bundle  Pathway seen in slide 7 o If electrode implanted in one of these regions, animal pressed robust learning, acquisition of brain stimulation reward behavior o Other chemicals are involved, not just dopamine o Behavior was strongly associated with dopamine because a major projection within circuitry is dopamine o Enhanced and robust increased dopamine levels within this brain circuitry o When dopamine antagonists are given to animal, animal will no longer press for stimulation reward Neurobiology of brain reward  DA = dopamine  Dopamine transmission within the primary rewards circuit mediates all positive rewarding stimuli including drugs and natural rewards  Drugs of abuse an hijack the system and induce neural adaptations that cause it to respond to drugs and natural rewards in pathological ways  Major evidence o Drugs of abuse can increase brain stimulaition award o Animal willing to lever press for lower levels of stimulation on drugs versus one that isn’t on drugs Cocaine Graph  Microdialysis technique o Dialysis membrane implanted and extract samples of cerebrospinal fluid o Dopamine levels (100% is baseline) o At time 0 injected with saline or cocaine o Robust increase ein extravellulr concentrations of dopamine as animal experiences effects of cocaine  See this effect with any drug of abuse Dopamine hypothesis of reward presents too simplified versions of events  Other systems are involved Slide 11  Studies carried out using MRI or PET  Stimulus is associated with brain activity….  Too simplistic to label dopamine as the pleasure molecule  ………..  Laboratory animals show enhanced dopamine release in response to anxiety and stress  Benzodiapines reduce dopa – perceived need mine levels  Blocking dopamine reduces negative emotional states o Dopamine is not all about positive responses o Is a very important mediator of rewarding effects of natural and unnatural rewards Addiction  Deleterious effects on user  Drug addiction leads to impulsive behaviors initially and compulsive behaviors  Once exposed to the drug, drug taking is not voluntary and becomes habitual (compulsive)  Drug abuse results in adverse consequences o Someone who abuses drugs doesn’t mean they are not substance dependent o Drug abuse suggests that individual is taking enough drug to have a negative effect in various parts of their life at a start Drug dependence – when drug is terminated, person experiences a negative psychological state  Physiological need for the drug is not necessarily associated with a psychological need for the drug  Can have a psychological need for drug without a physicological need  Continued need of drug whether that be physiological or psychological Drug addiction: psychological craving for the drug  Can have psychological motivation to take drug in absence of any physiological dependence Dependence  Physiological dependence – physical withdrawal syndrome when drug is removed  Psychological dependence – strong desire to experience ffects of drug because it produces pleasure or serves to reduce a negative emotional state o Able to have one or the other^^^ o Can have both  Drug addition/substance dependence disorder o Psychological dependence will always be manifest Psychotropc drugs  Hypnotics, alcohol, barbiturates, opiates, heroin, morphine o Strong physical and psychological dependence  Some drugs …………. o Nasal sprays, mixed agonist and antagonist opiates  Psychostimulates o Cocaine, amphetamine produce strong psychological dependence o When withdrawn, will suffer strong psychological withdrawal syndrome characterized by reduced ability to experience pleasure  Depression, negative emotional state  No physical symptoms  Antidepressants – do not induce either o Antipsychotic drugs Hyperalgesia – increased sensitivity to pain Analgesia – decreased sensitivity to pain Slide 23 o In text figure o X-axis = time o A – effect of intermittent administration of short acting drug o Systems able to recover between administrations o Termination of drug doesn’t result in withdrawal symtoms o B- same dose of short acting drug given at much closer time intervals, systems unable to recover between administrations of drugs, when drug is terminated, there will be a withdrawal symptom o mild o C- if same intervals accompanied by higher dose of drug o Magnitude of withdrawal symptom will be greater o Intensity and duration of drug and magnitude of withdrawal symptom have a direct correlation o D- longer acting drug given o Time intervals same as A, but organism doesn’t have same opportunity to recover before next administration, withdrawal symptom emerges o E- longer acting drug at shorter intervals, greater withdrawal symptom and longer duration of withdrawal Slide 22 o Takes time for dependence of a drug to develop o Following a single high dose in which organisms exposed to a high concentration of drug for as little as 12 hrs could result in an acute symptom of withdrawal o Strong negative emotional state in form of anhedonia – red
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