Roles for nigrostriatal--not just mesocorticolimbic--dopamine in reward and addiction

Abstract

Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson's disease who study the nigrostriatal dopamine system that originates in the substantia nigra (SN), and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal "systems" participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects of intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic terminal fields participates in the defining property of rewarding events: the reinforcement of memory consolidation. Thus, the similarities between nigrostriatal and mesolimbic dopamine systems can be as important as their differences.

Figure 1

Coronal sections of the ventral midbrain of the rat. (a) The blue line outlines the layer of dopaminergic cell bodies and dendrites (dark brown) as revealed by tyrosine hydroxylase immunohistochemistry. The green line outlines the GABAergic cell bodies (purple) of the substantia nigra pars reticulata as revealed by in situ hybridization. (b) In the same section, mRNA expression is shown for corticotropin-binding factor (white grain aggregates), a protein expressed in sub-populations of dopaminergic and GABAergic cells in regions with limbic and cortical projections: the VTA; the dorsal tier of SNc (a lateral extension of the parabrachial pigmented area of the VTA); and SNl (a regon projecting primarily to the amygdala). This protein is never expressed in the dopaminergic cells of the densocellular ventral tier of SNc (outlined in white), the origin of the nigrostriatal system, or in any of the cells of the SNr. (Note that the spacing of the cells in the dorsal and ventral tiers is not easily seen with TH immunohistochemistry, which labels dendrites as well as somata; the spacing is evident, however, from in situ hybridization or nissl-stained material: see [9], Fig. 3). Photomicrographs courtesy of Dr. Marisela Morales and Dr. Hui-Ling Wang; see [9] for full details.