Reward

Reward Psychopharmacology

• Rewards can be chemical or natural– food, exercise, sex, drugs

• Transiently or permanently alter neurochemical pathways– dopamine, serotonin, GABA, glutamate

• This subsequently alters psychological, physiological, and behavioral pathways

Reward Pathways….are complicated…………

1. Mesocorticolimbic:Ventral tegmental area (hindbrain)Nucleus accumbens (forebrain)Prefrontal Cortex

2. Mesopontine:Ventral tegmental area Pedunculopontine Tegmentum (hindbrain)

3. Nigrostriatal:Ventral tegmental area Substantia nigra (midbrain)Striatum (forebrain)

Reward pathways confer type of drug-seeking

These types of parameters are used tomeasure the extent of drug-seeking andlikelihood of full-blown addiction

Self-administering drugs

Hedonic Substitution: replacing one reward with another

Diverse Effects of Drugs of Abuse on Neurochemical Pathways

Heroin and Morphine (Opiates)

• Act on GABA and µ-opiod pathways, particularly, in the brain, on medium spiny neurons

Cocaine and Ecstasy (Psychostimulants)

• Act on dopamine and serotonin pathways, particularly on neurotransmitter reuptake transporters

For serotonin: cocaine and ecstasy block SERT

Nicotine and Caffeine (Psychostimulants)

• Act on cholinergic pathways, particularly increasing the rate and frequency of neuronal firing

Alcohol

• Acts on GABA and glutamate pathways, particularly by acting pre- or post-synaptically

The Effects of Gene Expression on Drug Intake (Neural Genetics)

Under-expression of Per2 enhances alcohol intake and craving

• We created mice that had normal Per2 transcription, but less PER2 translation

• Measured sleep/wake rhythms, circulating alcohol levels, and overall daily alcohol intake

Per2-mutant mice drink more alcohol and crave alcohol more often

….and higher circulating levels of alcohol at all hrs of the day

What about in humans?• Humans with certain single-nucleotide

polymorphisms of Per2 are more likely to become alcohol dependent