Reward, Reinforcement, and Addiction

Extinction doesn't erase fear memory but creates a new competing memory.
Hippocampus is vital for both fear expression and extinction.
Infralimbic (IL) cortex is needed for fear extinction, while prelimbic (PL) maintains fear.
Children and adolescents show differences in spontaneous recovery, cued extinction, and contextual conditioning related to vmPFC/IL and hippocampus.
Reconsolidating updates alter memory at the amygdala level, reducing fear memory recovery.
Several anxiety disorders exist, including PTSD, phobias, and generalized/social anxiety.
Stress induces physical/emotional/psychological strain (inverted U effects).
The hypothalamic–pituitary–adrenal (HPA) axis controls the release of stress hormones.
Glucocorticoid stress hormones can elevate anxiety.
Early life experiences can cause lasting changes in stress responses.
HPA response to stress is delayed and longer-lasting compared to the sympathetic nervous system.

Classical conditioning involves forming associations between conditioned stimulus (CS) and unconditioned stimulus (US).
Operant conditioning involves acquiring behaviors followed by a reinforcer.
Shaping involves gradually molding a target behavior by rewarding successive approximations.

Dopamine neurons originate in the VTA and SN (midbrain).
- VTA projects to the frontal cortex (mesocortical) and nucleus accumbens (mesolimbic).
- SN projects to the striatum (nigrostriatal pathway).
The medial forebrain bundle (MFB) contains fibers from the forebrain and brainstem, including the VTA.
Electrical stimulation of the MFB can have positive effects on mood.
Dopamine is necessary for brain stimulation to reinforce behavior.
Dopamine neurons fire:
- To unexpected reward (positive prediction error).
- To cues that predict reward.
- Decrease firing when expected reward is omitted (negative prediction error).
Nucleus accumbens is activated when subjects expect monetary gain (secondary reward).
The nucleus accumbens is strongly activated when subjects anticipate a large smile.
Dopamine strengthens connections between cortical and striatal neurons during reward learning.
A behavior that precedes a dopamine surge (unexpected reward) is reinforced.
An increase in glutamate receptors at the synapse increases likelihood that animal will press lever in future.

Dopamine is released from dopamine neurons and cleared by dopamine transporters.
Cocaine blocks dopamine reuptake, increasing dopamine levels in the synapse.
Amphetamine increases dopamine and norepinephrine release into the synapse.
Dopamine receptor blockers reduce the rewarding effects of cocaine.
Nicotine binds to nicotinic acetylcholine receptors in the VTA boosting dopamine release in the nucleus accumbens and prefrontal cortex.
Heroin, morphine, and oxycodone are opioid drugs that increase dopamine release in the nucleus accumbens.
Alcohol produces neuroadaptations, including DA hypoactivity.
Alcohol advertisements activate orbitofrontal cortex and ventral striatum.
Drug tolerance: reduced drug effectiveness with repeated use.
- Metabolic tolerance: body becomes better at ridding itself of the drug.
- Functional tolerance: reduced sensitivity of target sites.
- Conditioned tolerance: tolerance occurs only in the environment where the drug was taken.
Drug withdrawal includes mood changes, physical symptoms, and increased stress hormones.
Addiction is a vicious cycle of drug reinforcement, withdrawal, bingeing, and craving.
Inhibitory control depends on the prefrontal cortex; drugs of abuse impair prefrontal cortical function.
Korsakoff syndrome damages nerve cells and supporting cells in the CNS, and impacts memory both in acquiring and establishing new memories, and in retrieving previous memories.