Brain reward cascade -modified with permission from Gene Therapy Press. In this cascade, stimulation of the serotonergic system in the hypothalamus leads to the stimulation of delta/mu receptors by serotonin to cause a release of enkephalins. Activation of the enkephalinergic system induces an inhibition of GABA transmission at the substantia nigra by enkephalin stimulation of mu receptors at GABA neurons. This inhibitory effect allows for the fine tuning of GABA activity. This provides the normal release of dopamine at the projected area of the n. accumbens (reward site of the brain). It is noteworthy that other important neurotransmitters and receptors are involved such as endocannibinoids and glutamate.