The Central Nervous System
The communication between neurons can be distilled into six major steps of neurotransmission relevant to the neuropharmacology of addiction (Figure 2.3).
Step 1: Neurotransmitter synthesis, involving the molecular mechanisms of peptide precursors and enzymes for further synthesis or cleavage.
Step 2: Neurotransmitter storage.
Step 3: Neurotransmitter release from the axon terminal into the synaptic cleft (or from a secreting dendrite some cases).
Step 4: Neurotransmitter inactivation caused by removal from the synaptic cleft through a reuptake process, or neurotransmitter breakdown by
enzymes in the synapse or presynaptic terminal.
Step 5: Activation of the postsynaptic receptor, triggering a response of the postsynaptic cell.
Step 6: Subsequent signal transduction that responds to neurotransmitter receptor activation.
Drugs of abuse or drugs that counteract the effects of drugs of abuse can interact at any of these steps to dramatically or subtly alter chemical transmission to dysregulate or re-regulate, respectively, homeostatic function.
FIGURE 2.2 Neurons, synapses, and neurotransmitters. A typical example is shown for the neurotransmitter dopamine.
FIGURE 2.3 Synaptic neurotransmission. The figure shows a generalized process of synaptic transmission. (1) Various components of the neurotransmission machinery, such as enzymes, proteins, mRNA, and so on (depending on the neurotransmitter in question) are transported down the axon from the cell body. (2) The axonal membrane is electrically excited. (3) Organelles and enzymes in the nerve terminal synthesize, store, and release the neurotransmitter and activate the reuptake process. (4) Enzymes in the extracellular space and within the glia catabolize excess neurotransmitters released from nerve terminals. (5) The postsynaptic receptor triggers the response of the postsynaptic cell to the neurotransmitter. (6) Organelles within postsynaptic cells respond to the receptor trigger. (7) Interactions between genetic expression and postsynaptic nerve cells influence cytoplasmic organelles that respond to neurotransmitter action. (8) Certain steps are modifiable by events that occur at the synaptic contact zone. (9) The electrical portion of the nerve cell membrane integrates postsynaptic potentials in response to various neurotransmitters and produce an action potential. (10) The postsynaptic cell sends an action potential down its axon. (11) The neurotransmitter is released. The neurotransmitter that is released from the nerve terminal can be modulated by autoreceptors that respond to the neurotransmitter. [Modified with permission from Iversen LL, Iversen SD, Bloom FE, Roth RH. Introduction to Neuropsychopharmacology. Oxford, New York, 2009, p. 26.]