Distribution of CART (Cocaine- and Amphetamine-Regulated Transcript) Peptide in Mature and Developing Marsupial Brain

Abstract

CART (cocaine- and amphetamine-regulated transcript) is a neuromodulator involved in feeding, drug reward, stress and cardiovascular function. We have immunohistochemically studied the distribution of the CART peptide in the brains of two adult marsupial species: the brown antechinus (Antechinus stuartii) as a representative of polyprotodont marsupials and the tammar wallaby (Macropus eugenii) as a representative of diprotodont marsupials. We have also examined the distribution of CART during postnatal development in the tammar wallaby. There were similarities and differences both between the two marsupial species and between the marsupials and eutherians in CART distribution. Both marsupials showed immunoreactivity to CART in the olfactory bulb, piriform cortex, extended amygdala, the supraoptic, paraventricular and arcuate nuclei of the hypothalamus, somatosensory and auditory nuclei of the brainstem, vagal/solitary complex, raphe obscurus and raphe pallidus and presumptive presympathetic neurons of the ventrolateral medulla, as has been seen in eutherians. On the other hand, immunoreactivity to CART was weak in or absent from isocortical areas, and immunoreactivity to CART was poor or minimal in the ventral tegmental area and nucleus accumbens of both species; regions where immunoreactivity to CART is very strong in the brains of eutherians. During development, CART was present at birth (P0) in the lateral trigeminal ganglion, spinal trigeminal tract and the vagal sensorimotor complex, but did not appear in mid- or forebrain regions until much later (from P37). These anatomical findings indicate that although CART is likely to serve very similar functions in both eutherians and marsupials, there are potentially functionally significant differences between the two mammalian groups.

CART peptide following social novelty in the prairie vole (Microtus ochrogaster)

“…Of the fourteen regions examined, only one (the BNST) was sexually dimorphic, with males showing higher staining than females (Figure 2). This is consistent with previous research showing that while basal levels of CART peptide are generally not sexually dimorphic (prairie and meadow voles: Hunter et al, 2005a; rats: Balkan et al, 2006; brown antechinus: Ashwell and Mai, 2010), CART response to stimuli may be sexually dimorphic in a region-specific manner (Balkan et al, 2006; Gozen et al, 2007). Although our findings of a sex difference in the BNST may appear to conflict with previous work (Hunter et al, 2005a), it should be noted that this earlier report was qualitative in nature and due to small sample size did not use statistical analyses to verify the presence or absence of sex differences.…”

Immunohistochemical localization of cocaine‐ and amphetamine‐regulated transcript peptide (CARTp) in the brain of the pigeon (Columba livia) and zebra finch (Taeniopygia guttata)

“…D–H, ). We found CARTp‐ir in the anterior hypothalamus, PVN, ventromedial hypothalamus, and lateral hypothalamus, all areas that are also CARTp‐ir in mammals (Koylu et al, ; Hunter et al, ; Ashwell and Mai, ) and other vertebrates (Lázár et al, ; Roubos et al, ). Thus, hypothalamus expression of CARTp is highly conserved across vertebrate clades.…”

“…K,L, G,H). In contrast, CARTp‐ir is absent from the SN marsupial, and only weakly present in the VTA of one of the two species studied so far (Ashwell and Mai, ). Similarly, CARTp‐ir is only weakly present in the VTA of one of the two vole species studied, but is present in the SN of both (Hunter et al, ).…”

“…In the brain of mammals, CART peptides (CARTp) are expressed in several areas that have been related to the regulation of food intake, including the arcuate nucleus, the lateral hypothalamus, and the paraventricular nucleus (Couceyro et al, ; Koylu et al, , ; Hunter et al, ; Ashwell and Mai, ). This suggests a strong role of CARTp in the modulation of activity of neural circuits involved in the regulation feeding behavior, and several experiments support this idea (see Rogge et al, ; Lau and Herzog, for reviews).…”

“…CARTp structure is phylogenetically conserved (Murashita et al, ) and is expressed in the brains of marsupials (Ashwell and Mai, ) and several eutherian mammals, including humans (Couceyro et al, ; Koylu et al, , ; Charnay et al, ; Hunter et al, ), amphibians ( Rana esculenta, Lázár et al, ; Xenopus laevis, Roubos et al, ), teleosts (Kehoe and Volkoff, ; Singru et al, ; Murashita et al, ; Mukherjee et al, ; Volkoff, ), and an elasmobranch (MacDonald and Volkoff, ). Across these species, the localization of CARTp expression in the brain also appears to be highly conserved (e.g., subpallium, hypothalamus; reviewed in Subhedar et al, ).…”