The neurotransmitters affected are serotonin and norepinephrine. Dopamine itself is used as precursor in the synthesis of the neurotransmitters norepinephrine and epinephrine. Catechol-"O"-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The actions increase the synaptic concentrations of monoamine neurotransmitters. All of the other four neurotransmitters play a role in activating the acetylcholine neurons. Therefore, action potentials are triggered with lower levels of excitatory neurotransmitters. Acetylcholine may be one of the neurotransmitters involved in this pathway. The theory postulates that insufficient activity of monoamine neurotransmitters is the primary cause of depression. No reuptake inhibition of any of the neurotransmitters occurs. The distinction between excitatory and inhibitory neurotransmitters is not absolute. Many neuronal nAChRs can affect the release of other neurotransmitters. One of the major neurotransmitters involved in conditioned fear learning is glutamate. Ligands include substrates, inhibitors, activators, signaling lipids, and neurotransmitters. These include growth factors, cytokines and neurotransmitters. Ligand gated ion channels are responsive to certain molecules such as neurotransmitters.