Pharmacology of reward Flashcards
brain structures in brain reared pathway
1) VTA = dopamine releasing neurons at midline on floor of midbrain
2) VTA and nucleus accumbens = reward and reinforcement (interface limbic emotional-motivation and EP regal of motor)
3) amygdala = formation of stimulus-reward assoc
4) hippocampus = memory circuit for assoc btwn biologic stim (or drug) and environment
5) prefrontal cortex = exec function for control over impulses from destruction
structures inside nucleus accumbens, amygdala, hippocampus, lateral hypothal, prefrontal cortex all receive DA from where?
cell bodies in midbrain VTA
normal function of reward path
mediate pleasure perception (reward and strengthen behaviors assoc with natural reinforcers
reactive reward system consists of (3)
1) VTA = DA neuron cell bodies that respond to glut
2) nucleus accumbens = contains medium spiny neurons release GABA; site of DA neuron projection
3) amygdala = connection to both VTA and NA; house neurons release glut
function of reactive reward
signal immediate prospect of either pain (negative) or pleasure (positive) and provides motiv to achieve pleasure or avoid pain
ex= food, water, sex to activ reward
final common path of reinforcement and reward
pleasure NT?
mesolimbic dopamine pathway = VTA to nucleus accumbens = pleasure center
pleasure NT = dopamine
VTA activation releases ___ where
release DA on to nucleus accumbens neurons
define reinforcing stim
incr probability that behaviors paired will be more repeated
more intense and more direct effect on DA release, more addictive
dopaminergic neurons do not
signal ___
but they do signal ___
do not signal reward but signal even that warrants attention (learning)
what happens in repeated drug exposure
1) addictive drug = incr DA release more than natural
2) strong but inappropriate signal
3) plasticity in glut –> LTP –> strengthens connection btwn 2 neurons
quick and constant
4) also DA neurons in VTA respond to glut and recruited earliest during repeated drug exposure
repeated drug exposure results in ___ learning (pathway) to trigger drug seeking behavior with drug cues
pathologic learning
VTA –> amygdala
what happens after learning conditioned in amygdala
connection back to VTA = detector for anything relevant to prior drug experience
amygdala to nucleus accumbens –> signal emotion memories from internal/ext cues to initiate impulsive-automatic-obligatory actions to find drugs
Net result to drug addiction
reactive reward hijacks normal circuitry
tolerance develops to release of DA by normal biological stim
also, every use of drug = large release of DA to promote NEW LEARNING (new assoc btwn drug and environ or reinforce inapprop learning about drug cues with INCR GLUT)
dopamine hypothesis of addiction
drugs of abuse activate dopamine in mesolimbic system
more dopamine released or available at nucleus accumbens, more addictive
mechanisms of how DA levels can incr
1) GABAergic inhib (VTA)
2) reuptake inhib
3) ACh receptors
mechanisms of how DA levels can incr
GABAergic inhib
1) abuse drug hyperpol GABAergic neuron –> disinhibit DA neuron –> fire more –> release more DA
2) effects = decr anxiety, behavioral disinhib, sedation, euphoria
examples of GABAergic inhib
1) barbiturates
2) benzo
3) etoh
4) opiates
mechanisms of how DA levels can incr
reuptake inhib
allows DA and other monoamines to hang out longer in clef
mechanisms of how DA levels can incr
examples of reuptake inhib
cocaine
amphetamines (directly incr DA release)
mechanisms of how DA levels can incr
ACh receptors
mimic ACh at presynap nicotinic receptor site = excite DA neurons to release DA in nucleus accumbens
mechanisms of how DA levels can incr
ex of ACh receptor
Nicotine
drugs with abuse potential induce DA release to nucleus accumbens (more or less) than natural
more
drugs with abuse potential
rate of onset of action
incr abuse with faster onset
For cns, inhalation > IV > muc membrane > oral
drugs with abuse potential
inhalation route
benefits
ex drugs
can titrate blood levels pricely
cocaine, nicotine, meth, cannabis
