4: opioid reinforcement, tolerance, dependence

What are opioids significant reinforcing properties?

They enhance reward by decreasing the threshold for it

this happens again with the dopaminergic mesolimbic pathway, opioids in the VTA increase dopaminergic cell firing which increase DA release in NAcc

dopaminergic mesolimbic pathway

VTA → midbrain → NAcc

How exacly are opioids increasing dopaminergic cell firing in the VTA?

B-endorphin and opioid drugs increase VTA cell firing by inhibiting inhibitory GABA cells

*normally GABAergic neurons inhibit dopaminergic neurons

What do dynorphins do?

these are endogenous opioids which act on K receptors which then act on DA nerve terminals in the NAcc, decreasing DA causing dysphoria

Chronic use can lead to two things

tolerance or sensitization

Tolerance for opioids

Diminishes effecs of the drug with repeated exposure, for opioids this is only for the analgesic properties not pupil constriction or constipation

Sensitization for opioids

Increase in the drug effects, occurs with repeated administration
Ex: cravings not the pleasurable effects

liking vs wanting

also cross tolerance with other opioids

Physical dependence for opioids

Occurs w/t prolonged use, leads to neuroadaptive changes which then lead to withdrawal symptoms

opioids suppress CNS function, therefore withdrawal causes hyperactivity

When does opioid withdrawal peak? When does it end

36-48 hours and fully ends 7-10 days later

the withdrawal functions are opposite of acute actions

What is the opioid tolerance hypothesis?

start in homeostasis → take the drug disrupting homeostatis → this alters brain function to counteract the drug → this puts you back in homeostasis as long as you keep taking the drug → if you stop taking the drug your brain is out of homeostais again and unhappy