Origin of the dopaminergic innervation of the central extended amygdala and accumbens shell: A combined retrograde tracing and immunohistochemical study in the rat

Abstract

The origin of the dopaminergic innervation of the central extended amygdala (EAc; i.e., the lateral bed nucleus of the stria terminalis [BSTl]-central amygdaloid nucleus [Ce] continuum) and accumbens shell (AcSh) was studied in the rat by combining retrograde transport of Fluoro-Gold (FG) with tyrosine hydroxylase (TH) immunofluorescence. Perikaryal profiles (PP) immunoreactive to FG and to both FG and TH were counted in A8-A14 dopaminergic districts. Our results suggest that dopaminergic inputs to the EAc and AcSh arise from the ventral tegmental area-A10, substantia nigra, pars compacta-A9, and retrorubral nucleus-A8 groups as well as from the dorsal raphe nucleus and periaqueductal gray substance, housing the dorsocaudal part of A10 group (A10dc). Quantitative estimates reveal that the A10dc group contains approximately half of the total number of FG/TH double-labeled PP projecting to Ce and BSTl. By using an anti-dopamine serum, DR/PAG projections to Ce were confirmed to be in part dopaminergic. In contrast, modest numbers of FG/TH double-labeled PP were seen in the A10dc group after injections in the sublenticular extended amygdala, interstitial nucleus of the posterior limb of the anterior commissure or AcSh. Ventral mesencephalic projections to the EAc display a crude mediolateral topographic organization, whereas those to the AcSh are topographically organized along a mediolateral and an inverted dorsoventral dimension. The diencephalic dopaminergic groups do not innervate the EAc or AcSh, except for the periventricular gray-A11 which sends light dopaminergic projections to Ce and BSTl. Overall, the present results provide additional details on the organization of the mesolimbic dopaminergic system that critically controls behavioral responsiveness to salient environmental stimuli.

Role for Dopamine Neurons of the Rostral Linear Nucleus and Periaqueductal Gray in the Rewarding and Sensitizing Properties of Heroin

“…Considering these connections and the key role of dopamine on drug reward, RLi and PAG could participate in opiate reward. Besides, the number of amygdalopetal dopaminergic fibers arising from the PAG (and DR) is the same that those arising from A8, A9, and VTA-A10 groups together (Hasue and Shammah-Lagnado, 2002), and RLi/ PAG tyrosine hydroxylase TH + efferents course in the VTA and medial forebrain bundle (MFB) suggesting that they could also be affected after VTA and MFB dopaminergic lesions and participate in functional changes reported by different authors (Vertes, 1991).…”

“…The dopaminergic network of the RLi/PAG region is composed of three types of dopamine neurons: small RLi/ vPAG neurons, periaqueductal neurons of the PAG, and large-size PAG neurons, as reported by others (Hökfelt et al, 1976;Hasue and Shammah-Lagnado, 2002). NeuN labelling Values are expressed as percent mean7SEM with respect to a nondopaminergic background signal (commissure superior colliculi).…”

“…Many TH + fibers are seen running within the ventrolateral PAG in accordance with Peyron et al (1995), with regularly spaced synaptic varicosities resembling those observed in other dopaminergic areas such as dorsal striatum, suggesting the existence of a local circuit controlled by dopaminergic neurons. In this context, previous studies have described the presence of scattered dopaminergic neurons in the PAG with relatively short axons, along with larger TH + fibers projecting to different structures such as central amygdaloid nucleus and extended amygdala (Hökfelt et al, 1976;Grove, 1988;Hasue and Shammah-Lagnado, 2002). The presence of synaptic varicosities in the PAG has also been described (Buma et al, 1992).…”

“…The PAG/DR network is also termed the dorsocaudal A10 group (A10dc) (Hökfelt et al, 1984;Hasue and Shammah-Lagnado, 2002). Figure 1 shows representative mesencephalic sections including those nuclei with dopaminergic neurons.…”

“…The dopaminergic network of the PAG is composed of small and large neurons (Hasue and Shammah-Lagnado, 2002). Dopamine neurons of the RLi/PAG region project locally or onto different brain structures such as the central amygdaloid nucleus, bed nucleus of the stria terminalis, sublenticular extended amygdala, and substantia innominata (Ottersen, 1981;Grove, 1988;Hasue and Shammah-Lagnado, 2002). These neural areas are of relevance for drug reward, particularly the central amygdaloid nucleus and extended amygdala (Wise, 1989;Caine et al, 1995;Di Chiara et al, 1999;Nestler, 2001).…”