PBSI 336 Chapter 5: Addiction

midbrain, pons, medulla

brainstem

nucleus accumbens, caudate, and putamen

major striatum components

caudate

dorsomedial striatum

putamen

dorsolateral striatum

nucleus accumbens

(core and shell) pleasure, motivation, reward cues

dorsomedial striatum

goal directed actions

flexible, rapidly acquired behaviors

dorsolateral striatum

habits

inflexible, automatic behaviors

dopamine axon terminal in the brain

striatum is a major target of

brainstem

there are no dopamine neurons in striatum. the cell bodies are located in the

monoamine neurons

located primarily in the brainstem. cell bodies in brain stem but send axon projections throughout the brain

substantia nigra and ventral tegmental area

majority of dopamine neurons are in the

DA neurons in substantia nigra

nigrostriatal pathway source

dorsal striatum

nigrostriatal pathway target of axons

DA neurons in the VTA

mesolimbic and mesocortical pathway source

nucleus accumbens and amygdala

mesolimbic pathway target

prefrontal cortex

mesocortical pathway target

basal ganglia circuits are important for

voluntary movement

action selection

procedural learning

habits

major input structures are

glutaminergic (excitatory)

major output structures are

GABAergic (inhibitory)

excite targes of BG output

striatum projections direct pathways

inhibit targets of BG output

striatum projections indirect pathways

midbrain dopamine and thalamus

provide feedback in the system and complete the loops

D1 receptors and D2 receptors

in the striatum, half of GABA neurons express ____ and the other half express ____

activated by dopamine

D1 neurons are part of the direct pathway which is

inhibited by dopamine

D2 neurons are part of the indirect pathway which are

dopamine, although via different mechanisms

all addictive drugs share the common property of increasing

liking, wanting, reward prediction

components of reward learning

liking

affective/hedonic/pleasurable aspects of reward (does NOT involve DA)

wanting

motivational/incentive drive to obtain reward (involves DA)

reward prediction

learning about cues/actions related to reward (involves DA)

reward is given unexpectedly

temporary increase in firing rate (dopamine neurons)

conditioned stimulus and reward

temporary increased firing after DS, not reward

conditioned stimulus with no reward

temporary increase, then temporary decrease. reward prediction error

positive prediction error

increased activity with unexpected reward (outcome better than expected)

zero prediction error

unchanged baseline activity for fully predicted reward (outcome was as expected)

negative prediction error

depressed activity with unexpected reduction of reward (outcome worse than expected)

dopamine

serves as a teaching signal for learning about reward

D1 cells and direct pathway

positive prediction error activates

D2 cells and indirect pathway

negative prediction error activates

properties of drugs, individual differences, drug induced neuroadaptations

factors influencing addiction vulnerability

compulsive seeking of drugs and craving/relapse of drugs

what is addiction

properties of the drug that affects propensity to develop addiction

route of administration

lipid solubility

individual differences

genes contributing to addiction vulnerability or resilience

individual differences

environment/psychosocial factors

individual differences

complex interactions between genes and environment

increased addiction likelihood

high impulsivity, history of stress/trauma

decreased addiction likelihood

environmental enrichment

reduced D2 receptor availability in striatum

correlated with impulsivity in meth abusers

animals that have a high level of premature/impulsive responding

decreased D2 binding in ventral striatum

cocaine

impulsivity may be a pre-existing condition for addiction

stress

influences all aspects of the addiction process

low-dose cocaine

rats with a history of social defeat stress showed greater CPP for

environmental enrichment

reduced CPP for cocaine

prefrontal cortex

behavioral inhibition

self control; executive function

resolving conflict in behaviors

habit

stimulus-response association

goal-directed

response-outcome association

habit learning

chronic stress causes enhanced

PFC volume and reduced dendritic complexity

chronic stress causes loss of

neuronal density in dorsal striatum

chronic stress changes

sensitization of drug effects

enhanced habit learning

reduced behavioral inhibition

drug induced factors that increase addiction likelihood

followed by abstinence

animal self administration model with intermittent cocaine use

increased cocaine potency and increased drug motivation

animal self administration model results in

habitual responding

history of cocaine exposure biased toward

more PCF activity

more self control

less PFC activity

less self control