This is also due to alcohol's effect on the opioid systems, or endorphins, that have opiate-like effects, such as modulating pain, mood, feeding, reinforcement, and response to stress. Antidepressants Antidepressants reduce symptoms of mood disorders primarily through the regulation of norepinephrine and serotonin (particularly the 5-HT receptors). After chronic use, neurons adapt to the change in biochemistry, resulting in a change in pre- and postsynaptic receptor density and second messenger function. The use of antidepressants originates from the Monoamine Theory of Depression and Anxiety, which states that the disruption of the activity of nitrogen containing neurotransmitters (i.e. serotonin, norepinephrine, and dopamine) is strongly correlated with the presence of depressive symptoms. Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressants. They inhibit monoamine oxidase, the enzyme that metabolizes the monoamine neurotransmitters in the presynaptic terminals that are not contained in protective synaptic vesicles. The inhibition of the enzyme increases the amount of neurotransmitter available for release. It increases norepinephrine, dopamine, and 5-HT, thus increasing the action of the transmitters at their receptors. MAOIs have been somewhat disfavored because of their reputation for more serious side effects. Tricyclic antidepressants (TCAs) work through binding to the presynaptic transporter proteins and blocking the reuptake of norepinephrine or 5-HT into the presynaptic terminal, prolonging the duration of transmitter action at the synapse. Selective serotonin reuptake inhibitors (SSRIs) selectively block the reuptake of serotonin (5-HT) through their inhibiting effects on the sodium/potassium ATP-dependent serotonin transporter in presynaptic neurons. This increases the availability of 5-HT in the synaptic cleft. The main parameters to consider in choosing an antidepressant are side effects and safety. Most SSRIs are available generically and are relatively inexpensive. Older antidepressants such as TCAs and MAOIs usually require more visits and monitoring, which may offset the low expense of the drugs. SSRIs are relatively safe in overdoses and better tolerated than TCAs and MAOIs for most patients. Antipsychotics All proven antipsychotics are postsynaptic dopamine receptor blockers (dopamine antagonists). For an antipsychotic to be effective, it generally requires a dopamine antagonism of 60%–80% of dopamine D2 receptors. First generation (typical) antipsychotics: Traditional neuroleptics modify several neurotransmitter systems, but their clinical effectiveness is most likely due to their ability to antagonize dopamine transmission by competitively blocking the receptors or by inhibiting dopamine release. The most serious and troublesome side effects of these classical antipsychotics are movement disorders that resemble the symptoms of Parkinson's disease, because