Shown at right is a coronal section through the upper brain stem of a human brain. In the center is the substantia nigra where dopamine cell bodies are located. The dark staining results from the deposition of melanin and marks dopaminergic cell bodies. From The Human Brain, Henri Duvernoy; New York: Springer-Verlag Wien, 1991.

Shown at right is a photomicrograph of the human substantia nigra. The location of various groups of dopamine cell bodies are in this region. Legend: Aq=cerebral aqueduct, CG=central gray, cp=cerebral peduncle, d=dorsal, DR=dorsal raphe nucleus, m=medial, MG=medial geniculate, mlf=medial longitudinal fasciculus, PBP=parabrachial pigmented nucleus, PN=paranigral nucleus, R=red nucleus, RLi=rostral linear nucleus, SC=superior colliculus, SNC=substantia nigra pars compacta, 3= oculomotor nucleus, 3n=oculomotor nerve axon. From The Human Nervous System ed. G. Paxinos; Chapter 31, "Catecholaminergic Neurons", John Pearson, Glend Halliday, Noboru Sakamoto, and Jean-Philippe Michel; San Diego: Academic Press, 1990.

Shown at right is a coronal section through the cerebrum of a human brain. In the center is located the anterior striatum, including the caudate nucleus (medial) and putamen (lateral) separated by the internal capsule. Many dopamine fibers terminate in this region. From Atlas of the Human Brain in Section, 2nd ed., Melville Roberts, Joseph Hanaway, and D. Kent Morest; Philadephia: Lea & Febiger, 1987.

The photomicrograph at right displays [3H]WIN35428 binding to the dopamine transporter in the striatum, at a level similar to that shown above. The density of dopamine transporter binding sites are increased in cocaine users. From "Cocaine use increases [3H]WIN 35428 binding sites in human striatum", Little et al. Brain Res. 628:17-25, 1993.

Shown at right is a photomicrograph of [125I]RTI-121 binding in human amygdala. Ongoing sudies are evaluating the effects of cocaine in this region. Legend: BL=basolateral n, pc=pars compacta (small cell part) of basolateral n., Lat=lateral n., BM=basomedial n., CO=cortical n., Un=uncus, HC=hippocampus. This picture is reproduced from "Characterization and Localization of [125 I]RTI-121 binding sites in Human Striatum and Medial Temporal Lobe", K. Little, F. Carroll, and B. Cassin; J Pharmacol Exp Ther 274:1473-1483, 1995.

Shown at right is a photomicrograph demonstrating dopamine transporter messenger RNA distribution in human midbrain. Legend: MedDA=medial dopaminergic cells (including paranigral nucleus and posterior medial substantia nigra compacta), LatDA=leteral dopameniergic cells (including posterios lateral and posterior superior substantia nigra compacta). This picture is reproduced from "Brain Dopamine Transporter Messenger RNA and Binding Sites in Cocaine Users", Little et al; Arch Gen Psych 55: 793-799, 1998.

At right, striatal [3H]WIN 35428 binding to the dopamine transporter was increased in cocaine users vs. matched control subjects in 3 regions (unpaired t tests between cocaine users and controls: asterisk, P<.001; dagger, P<.05). Average cocaine values increased by 43% (caudate), 40% (putamen), and 45% (accumbens). Assay was performed at a saturating concentration of [3H} WIN 35428 (100nmol) by quantitative autoradiography. This picture is reproduced from "Brain Dopamine Transporter Messenger RNA and Binding Sites in Cocaine Users", Little et al; Arch Gen Psych 55: 793-799, 1998.

The specific role of dopamine neurons in reward in uncertain, some of the postulated theories are listed at right. An excellent reference is: "What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?", K. Berridge and T. Robinson, Brain Res Rev 28:309-369, 1998. Our experiments showing alterations in dopamine neurons could explain disturbed motivation in addicts.