1. Reward

2. 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

3. 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)

4. Reward pathways confer type of drug-seeking These types of parameters are used to measure the extent of drug-seeking and likelihood of full-blown addiction

5. Self-administering drugs

6. Hedonic Substitution: replacing one reward with another

7. Diverse Effects of Drugs of Abuse on Neurochemical Pathways

8. Heroin and Morphine (Opiates) Act on GABA and µ-opiod pathways, particularly, in the brain, on medium spiny neurons

9. Cocaine and Ecstasy (Psychostimulants) Act on dopamine and serotonin pathways, particularly on neurotransmitter reuptake transporters For serotonin: cocaine and ecstasy block SERT

10. Nicotine and Caffeine (Psychostimulants) Act on cholinergic pathways, particularly increasing the rate and frequency of neuronal firing

11. Alcohol Acts on GABA and glutamate pathways, particularly by acting pre- or post- synaptically

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

13. 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

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

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

16. What about in humans? Humans with certain single-nucleotide polymorphisms of Per2 are more likely to become alcohol dependent