The basic mechanisms by which different substances activate the reward system are as described above, but vary slightly among drug classes.[13].
Depressants
Depressants such as alcohol, barbiturates, and benzodiazepines work by increasing the affinity of the GABA receptor for its ligand; GABA. Narcotics such as morphine and methadone, work by mimicking endorphins—chemicals produced naturally by the body which have effects similar to dopamine—or by disabling the neurons that normally inhibit the release of dopamine in the reward system. These substances (sometimes called "downers") typically facilitate relaxation and pain-relief.
Stimulants
Stimulants such as amphetamines, nicotine, and cocaine, increase dopamine signaling in the reward system either by directly stimulating its release, or by blocking its absorption (see "reuptake"). These substances (sometimes called "uppers") typically cause heightened alertness and energy. They cause a pleasant feeling in the body, and euphoria, known as a high. This high wears off leaving the user feeling depressed. This sometimes makes them want more of the drug, and can worsen the addiction.
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