Drug addiction and the brain reward system

Drug addiction and the brain reward system 組員:Sam Wang王煜豪 Pony Lien連顥庭

brain reward system • Reward-- positive value of an internal physical state • Incentive motivation Affect (Want) (Like) • Incentive salience (Brain’s dopamine system) (Incentive salience)

Incentive motivation • Psychological reward • Anatomy • Modulation by drugs

Psychological reward • modification of behavior sensory properties of rewards. more effective than punishment in enforcing positive behavior • Ex:altruism

Anatomy • Dopamine mesolimbic pathway mesocortical pathway

Ventral Tegmental Area(VTA) • Region near the base of the brain • Inputs of the reward system • Releasing Dopamine • mesolimbic pathway Inhibitory neuron Dopamine releasing VTA neuron Cerebral neuron of reward pathway

Dopamine stimulate (D1 Receptor) inhibit (D2 Receptor)

Modulation by drugs • increase the dopamine release • Arises psychological drug tolerance , sensitization. Psychological drug tolerance • CREB protein • delta FosB activating genes causes sensitization. intense cravings (associated with drug addiction) extend the peripheral cues of drug use

Drug Addiction • Impulsive, destructive behavior medication • Can’t help taking medicine • 3 major reasons to lead to drug addiction • 1.Hyperactive incentive system • 2.Uncomfortable withdrawal symptoms • 3.Permanent change in incentive system

Hyperactive incentive system • Most of drugs can lead to hyperactive incentivesystem. • They act on Brain’s dopamine system directly,so they can make mesolimbic pathwaymore vigor

Uncomfortable withdrawal symptoms • Tolerance:need more medicaine to reach the general level of joy. • Withdrawal: the unpleasant effects of getting used to not taking a drug that they have become dependent on

Permanent change in incentive system • Neural sensitization: dopamine nerve cells were activated easily by drugs.

Cocaine • obtained from the leaves of the coca plant • stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic • The decreased dopaminergic signaling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine

Amphetamine • psychostimulant drug • increased wakefulness and focus • decreased fatigue and appetite • vesicular level • dopamine transporter DAT • reverse tolerance • sensitization to psychological • locomotor-stimulating effects • benzodiazepines • Barbiturates

Cocaine binds directly to the DAT transporter, inhibiting reuptake with more efficacy than amphetamines which phosphorylate it causing internalization; instead primarily releasing DAT (which cocaine does not do) and only inhibiting its reuptake as a secondary, and much more minor, mode of action than cocaine and in another manner: from the opposite conformation/orientation to DAT.

Heroin • Diamorphine • from morphine • 3-monoacetylmorphine 6-monoacetylmorphine • μ-opioid agonists morphine 6-MAM • a strong analgesic deacetylated

Morphine • name from the Greek god of dreams Morpheus • is a potent opiate analgesic medication • Can be used as an analgesic to relieve • can be taken orally, rectally, subcutaneously, intravenously, intrathecally or epidurally

Drug addiction and the brain reward system