Key Concepts
     1. Many substances have been identified as neurotransmitters according to formal criteria. Many more putative transmitters are being evaluated, so the total number of confirmed transmitters is likely to continue to grow.
     2. Each step in synaptic transmission, from axonal transport to postsynaptic effects, is a potential target for neuropharmacological compounds.
     3. The search for new drugs and the characterization of new types of receptors occur in parallel. Sometimes a brain receptor for a particular exogenous drug is discovered; the existence of such a receptor implies that the brain makes an endogenous ligand for that receptor.
     4. Although drugs frequently have higher affinity for a particular type of receptor than for other types, the “tuning” of drugs tends to be somewhat nonspecific. Most drugs, if present in the body in sufficiently high concentration, will bind to many different types of receptors.
     5. Drugs may affect many different aspects of presynaptic function, such as alteration in transmitter synthesis, alteration in transmitter storage, alteration in transmitter release, alteration in autoreceptor function, blockade of reuptake, and inhibition of breakdown enzymes.
     6. Drugs may affect many different aspects of postsynaptic function, including activation of postsynaptic receptors, blockade of postsynaptic receptors, alteration in second messenger activity, alteration in gene expression, and up- and down-regulation of postsynaptic receptor density.
     7. Repeated use of some drugs causes the development of tolerance: Repeated doses of the same size have less and less effect.
     8. Repeated use of some drugs causes the development of sensitization: Repeated doses of the same size have greater and greater effect.
     9. Endogenous opiates such as morphine are powerful analgesics and have considerable abuse potential. Several different types of opiate receptors have now been identified, along with a number of endogenous opiate peptides.
     10. The existence of cannabinoid receptors in the brain, through which THC has its effects, implies the existence of an endogenous ligand, which may be anandamide.
     11. In some cases stimulant drugs act by mimicking the effects of a neurotransmitter; other stimulants act by directly or indirectly altering the concentration of neurotransmitter in the synapse; still others act by altering the actions of neuromodulators such as adenosine.
     12. Hallucinogenic drugs alter sensory perceptions rather than provoking true hallucinations. Some hallucinogens act by interacting with serotonin receptors, but much remains unknown about the physiological bases of the effects of these drugs.
     13. Chronic alcohol abuse alters both the function and structure of the brain. Happily, these effects are largely reversible following cessation of the use of alcohol.
     14. Several models of drug abuse have been proposed, none of which explains all of the phenomena associated with dependency. The positive reward model has received strong support from drug self-administration studies.
     15. Animal models of drug abuse have been successfully developed because animals will frequently choose to ingest psychoactive substances and respond to those substances in ways that are similar to human responses.
     16. Recent advances in our understanding of the neurophysiological bases of drug abuses have led to proposals of several pharmacological interventions for the treatment of substance-related disorders.