Efferent connections of the substantia nigra and ventral tegmental area in the rat

Beckstead, Robert M.; Domesick, Valerie B.; Nauta, Walle J. H.

doi:10.1016/0006-8993(79)91001-1

Cited by 1,195 publications

(360 citation statements)

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“…The highly circumscribed activation at the electrode site within the VTA, which continues rostrally within a rather compact zone of activity, is congruent with the well-described meso-telencephalic dopamine fibers that project dorsally and rostrally via the lateral aspect of the medial forebrain bundle and extend along the diagonal band of Broca to the level of the preoptic area (16). Furthermore, the pattern of activation in the forebrain terminal areas corresponds with the topography and innervation pattern of medially located dopamine cells in the VTA, as determined by histochemical mapping (17,18) and retrograde and anterograde tracing techniques (19,20). These anatomical studies have shown that these VTA A10 cells project rostrally to selectively innervate medial telencephalic structures, such as the lateral septum and nucleus accumbens, before proceeding rostrally to terminate in the deep layers (V and VI) of the anteromedial prefrontal cortex while avoiding more lateral structures such as the striatum (for review, see ref.…”

Section: Discussionmentioning

confidence: 90%

“…The bilateral activation in the hippocampus may also be due to indirect non-dopamine transynaptic inputs, possibly originating from the raphe nuclei. The pattern of metabolic activation caudal to the stimulation site corresponds to the descending efferents from the VTA that terminate in the ventral half of the central gray substance, including the dorsal raphe, parabrachial area, and the locus coeruleus (19). (24) on the basis of bilateral comparison of tracer concentrations in corresponding regions ipsilateral and contralateral to the stimulation.…”

Section: Discussionmentioning

confidence: 99%

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Changes in local cerebral glucose utilization during rewarding brain stimulation.

Esposito¹,

Porrino²,

Seeger³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The quantitative 2-deoxy[14C]glucose method was used to determine local cerebral glucose utilization in unrestrained rats responding (lever-press) for rewarding electrical stimulation to area A10 (ventral tegmental area) and in similarly implanted inactive controls. Self-stimulation was associated with significant increases in metabolic activity, highly circumscribed in the ventral tegmental area, that continued rostrally within a rather compact zone of activity through the medial forebrain bundle, extending via the diagonal band of Broca to the level of the preoptic area. In the forebrain terminal areas bilateral increases in local cerebral glucose utilization were noted in the nucleus accumbens, lateral septum, hippocampus, and the mediodorsal nucleus of the thalamus. Ipsilateral (i.e., side of stimulation) increases in glucose utilization were noted in the bed nucleus of the stria terminalis, the basolateral and central amygdaloid nuclei, and the medial prefrontal cortex. Caudal to the stimulation site, increases in glucose utilization were found in the midline dorsal raphe, the ipsilateral pontine gray, medial parabrachial nucleus, and the locus coeruleus. Significant bilateral increases were noted in various sensory and motor areas. These results indicate that rather than a diffuse pattern of activity, rewarding brain stimulation is associated with discrete activation of specific neuronal projection fibers and selective terminal sites.The discovery that rats will work to receive brief trains of electrical stimulation to discrete areas of their brains (1) was soon followed by similar demonstrations in diverse species from goldfish to higher primates, including man (2). This phenomenon has generally been interpreted as reflecting a very fundamental neurophysiological mechanism(s) of widespread and adaptive evolutionary significance (3)(4)(5). Early attempts to delineate the critical neural circuitry that mediates the reinforcing or rewarding aspects of this behavior yielded little specific information (6,7). Subsequent studies, however, suggested an important relationship between certain ascending catecholaminergic pathways and this behavior (8, 9). In particular, cogent evidence has been adduced for a critical, albeit nonexclusive, role for ascending dopaminergic fibers in the mediation of self-stimulation derived from cell bodies in the ventral tegmental area (VTA) (9), corresponding to area A10 of Dahlstrom and Fuxe (10). Because of the ability of the 2-deoxy[14C]glucose autoradiographic method to assess local metabolic and functional neural activities simultaneously throughout the entire brain (11), it was used in this study to examine the overall pattern of sensory, motor, and integrative neural activity during rewarding selfstimulation to the VTA. MATERIALS AND METHODSMale albino Sprague-Dawley rats (-350 g) were anesthetized with chloral hydrate and stereotaxically implanted unilaterally with bipolar platinum electrodes (0.125 mm diameter) aimed at the VTA (coordinates: A + 3.4, L ± 1.0, V + 2....

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Changes in local cerebral glucose utilization during rewarding brain stimulation.

Esposito¹,

Porrino²,

Seeger³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…In (18,19) but not biochemical approaches (20) (1992) i autoreceptors on perikarya and terminal areas of a subpopulation of dopamine neurons.…”

Section: Discussionmentioning

confidence: 99%

Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin.

Lévesque

Díaz

Pilon

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

549

321

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We have identified ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 100-, 1000-, and 10,000-fold lower at D2, D4, and D, receptors, respectively. Specific [3H]7-OH-DPAT binding sites, with a Kd of0.8 nM and a pharmacology similar to those at reference D3 receptors of CHO cells, were identified in rat brain. D3 receptors differ from D2 receptors in brain by their lower abundance (2 orders of magnitude) and distribution, restricted to a few mainly phylogenetically ancient areas-e.g., paleostriatum and archicerebellum-as evidenced by membrane binding and autoradiography studies. Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding. These various features suggest that D3 receptors are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons.Dopamine is an important neurotransmitter in brain, being involved physiologically in the control of cognitive, motor, and endocrine processes and pathologically in Parkinson and possibly mental diseases.Until recently, it was largely believed that its various actions were mediated by two receptor subtypes, termed D1 and D2 (1, 2). Molecular biology approaches have led, however, to the identification and cloning of the genes corresponding not only to these two receptor subtypes (3-7) but also to additional and less expected ones, termed D3 (8), D4 (9), and D5 (10, 11). For the latter receptors, the information so far available derives from molecular biology approaches; their pharmacology and signaling system have only been studied in transfected cells, generally fibroblasts, and their distribution has been indirectly approached by studies of mRNA localization. Nevertheless, these otherwise valuable approaches suffer from some limitations. When expressed in fibroblasts, receptors might find a membrane environment, which could modify their pharmacological specificity, and a repertoire of cellular components, particularly GTP-binding proteins (G proteins), which may differ from that found in neurons. Regarding distribution, mRNA detection reveals the sites of receptor synthesis rather than receptor localization, which may be different. Therefore, there is an obvious interest in studying the native receptor protein in brain, particularly in the case ofthe D3 receptor, whose pharmacology in Chinese hamster ovary (CHO) cells and cerebral localization of its mRNA suggest that it may represent an important target for antipsychotics (8,12,13).Starting with the idea that designing a selective radioactive probe for the D3 receptor would help to settle these issues, we have screened a series of dopamine agonists and thereby identified 7-hydroxy-N,...

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“…The dopaminergic neurons are mainly located in the ventral tegmental area (VTA) (Beckstead, Domesick, & Nauta,1979) and project primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy). These dopaminergic projections form five mesocorticolimbic dopaminergic neural pathways (Swanson, 1982).…”

Section: Introductionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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BackgroundThe mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well‐established depressogenic stressors, and they were proven to induce different depressive phenotypes.MethodsThe depressive and anxiety‐like behaviors of MD and CUPS‐treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1‐5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real‐time PCR and Western blot, respectively.ResultsSevere anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1‐/D2‐like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.ConclusionDifferent depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA‐NAc and VTA‐OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA‐PFC and VTA‐AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA‐PFC and VTA‐ST pathways.

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Efferent connections of the substantia nigra and ventral tegmental area in the rat

Cited by 1,195 publications

References 55 publications

Changes in local cerebral glucose utilization during rewarding brain stimulation.

Changes in local cerebral glucose utilization during rewarding brain stimulation.

Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin.

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

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