Ribeiro do Couto, Bruno

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Ribeiro do Couto, Bruno

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Anatomía Humana y Psicobiología

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Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
(MDPI, 2021-03-18) Guerrero-Bautista, Rocío; Franco-García, Aurelio; Hidalgo, Juana M.; Fernández-Gómez, Francisco José; Núñez, Cristina; Ribeiro do Couto, Bruno; Milanés Maquilón, María Victoria; Farmacología; Anatomía Humana y Psicobiología
Open Access
Multi-neuromeric origin of tyrosine hydroxylase-positive neurons within the substantia nigra and ventral tegmental area
(Frontiers Media, 2025-05-30) Ferrán Bertone, José Luis; Lucero-Arteaga, Franco; Ayad, Abdelmalik; Kutsenko Shchegolska, Yevheniy; Alonso Fuentes, Antonia; Ribeiro do Couto, Bruno; García-Cabezas, M.Á.; Tseng, Kuei Y.; Anatomía Humana y Psicobiología; Facultad de Medicina
During early developmental stages, the brain is divided into three primary regions: the forebrain (prosencephalon), the hindbrain (rhombencephalon), and the spinal cord. These regions are further segmented into transverse units called neuromeres, each with distinct molecular identities that guide their specialization through development. Such modular organization is evolutionarily conserved and shapes the structural and functional complexity of the brain. The substantia nigra (SN) and ventral tegmental area (VTA) are key midbrain regions involved in reward, motivation, and motor control. They contain dopamine-producing tyrosine hydroxylase (TH)-positive neurons, which are historically classified into three anatomical groups—A8 (retrorubral field), A9 (SN pars compacta), and A10 (VTA)—each with distinct anatomical and functional properties. Recent studies revealed further sub-regional organization along medial-lateral and anterior–posterior gradients, suggesting specialized roles tied to their developmental origins. This study uses the prosomeric framework to map the segmental distribution of TH-positive neurons within the SN and VTA across different mammalian species and developmental stages. Using a comparative analysis of rodent, non-human primate and human specimens, we were able to demonstrate that TH-positive neurons within the SN and VTA exhibit a multi-neuromeric organization, with neuronal populations distributed across the diencephalic prosomeres (dp1-dp3), the midbrain prosomeres (mp1-mp2) and the isthmic rhombomere (r0). It is therefore conceivable that such multi-neuromeric origin of TH-positive neurons within the SN and VTA likely influence the patterns of connectivity and functional specialization of the dopamine system.
Open Access
Sex‑dependent effects of forced exercise in the body composition of adolescent rats
(Nature Research, 2021-05-12) Kutsenko Shchegolska, Yevheniy; Barreda, A.; Toval Sánchez, José Ángel; Garrigos, D.; Martínez Morga, Marta; Ribeiro do Couto, Bruno; Ferrán Bertone, José Luis; Anatomía Humana y Psicobiología; Facultad de Medicina
Determining the body composition during adolescence can predict diseases such as obesity, diabetes, and metabolic syndromes later in life; and physical activity became an effective way to restore changes in body composition. However, current available literature assessing the body composition before, during and after adolescence in female and male rodents by in vivo techniques is scarce. Thus, by using computerized tomography, we aimed to define the baseline of the weight and body composition during the adolescence and young adulthood of female and male Sprague–Dawley rats (on P30, P60 and P90) under standard diet. Then, we determined the effect of 18 days of forced exercise on the body weight and composition during the early adolescence (P27-45). The highest percentual increments in weight, body volume and relative adipose contents occurred during the female and male adolescence. Forced running during the early adolescence decreased weight, body volume and relative adipose delta and increment values in males only. The adolescence of rats is a period of drastic body composition changes, where exercise interventions have sex-dependent effects. These results support a model that could open new research windows in the field of adolescent obesity.
Open Access
Prosomeric hypothalamic distribution of tyrosine hydroxylase positive cells in adolescent rats
(Frontiers Media, 2022-05-06) Bilbao, María G.; Garrigos, Daniel; Martínez Morga, Marta; Toval, Ángel; Kutsenko Shchegolska, Yevheniy; Bautista, Rosario; Barreda, Alberto; Ribeiro do Couto, Bruno; Puelles López, Luis; Ferrán Bertone, José Luis; Anatomía Humana y Psicobiología
Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region lies ventrally within the diencephalon, which includes preoptic, anterior, tuberal, and mamillary anteroposterior regions, and sometimes identifying dorsal, intermediate, and ventral hypothalamic partitions. This model is weak in providing little or no experimentally corroborated causal explanation of such subdivisions. In contrast, the modern prosomeric model uses different axial assumptions based on the parallel courses of the brain floor, alar-basal boundary, and brain roof (all causally explained). This model also postulates that the hypothalamus and telencephalon jointly form the secondary prosencephalon, separately from and rostral to the diencephalon proper. The hypothalamus is divided into two neuromeric (transverse) parts called peduncular and terminal hypothalamus (PHy and THy). The classic anteroposterior (AP) divisions of the columnar hypothalamus are rather seen as dorsoventral subdivisions of the hypothalamic alar and basal plates. In this study, we offered a prosomeric immunohistochemical mapping in the rat of hypothalamic cells expressing tyrosine hydroxylase (TH), which is the enzyme that catalyzes the conversion of L-tyrosine to levodopa (L-DOPA) and a precursor of dopamine. This mapping was also combined with markers for diverse hypothalamic nuclei [agouti-related peptide (Agrp), arginine vasopressin (Avp), cocaine and amphetamine-regulated transcript (Cart), corticotropin releasing Hormone (Crh), melanin concentrating hormone (Mch), neuropeptide Y (Npy), oxytocin/neurophysin I (Oxt), proopiomelanocortin (Pomc), somatostatin (Sst), tyrosine hidroxilase (Th), and thyrotropin releasing hormone (Trh)]. TH-positive cells are particularly abundant within the periventricular stratum of the paraventricular and subparaventricular alar domains. In the tuberal region, most labeled cells are found in the acroterminal arcuate nucleus and in the terminal periventricular stratum. The dorsal retrotuberal region (PHy) contains the A13 cell group of TH-positive cells. In addition, some TH cells appear in the perimamillary and retromamillary regions. The prosomeric model proved useful for determining the precise location of TH-positive cells relative to possible origins of morphogenetic signals, thus aiding potential causal explanation of position-related specification of this hypothalamic cell type.
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Elucidating the neuromeric organization of the Mongolian gerbil brain
(Springer, 2025-11-04) Lucero-Arteaga, F.; Labegorra, S.; Abrego-Álvarez, A.; Heck, V.; Portu, A. I.; Boeris, M. A.; Alonso Fuentes, Antonia; Ribeiro do Couto, Bruno; García-Cabezas, M. Á.; Tseng, K. Y.; Ferrán Bertone, José Luis; Anatomía Humana y Psicobiología; Facultad de Medicina
The Mongolian Gerbil (Meriones unguiculatus) diverged from rats/mice around 45 million years ago and developed adaptations to extreme temperatures and water scarcity. Another feature of the Mongolian Gerbils is their social monogamy similar to that of prairie voles. These observations suggest that there are potential differences in the Mongolian Gerbil brain that are distinct from that of rats and mice. The goal of the present study is to establish the extent to which the neuromeric organization of the brain is conserved in the Mongolian Gerbil and to gain insights on how evolutionary expansion and diversification of brain regions occur across species. Our data shows that the multineuromeric origin of tyrosine hydroxylase-positive processes in the Mongolian Gerbil is similar to that in mice and rats, spanning from the diencephalon, midbrain, and the rostral hindbrain. There are also observable anatomical differences. However, most of the components characteristic of these neuromeres are identifiable in the Mongolian gerbil, closely mirroring those found in mice and rats. Together, these findings suggest that the conserved neuromeric organization likely stems from a restricted genetic toolset that began in the Muridae family 45 million years ago, and that a profound reorganization of the fundamental structural plan delineating the neuromeric segmentation is not required for the emergence of diverse functionality among species of phylogenetically related families. Future studies are needed to establish how the genetic programs within each neuromeric unit are influenced by environmental factors that ultimately impact the size of the neuromeric derivatives and their functional connectivity.
Open Access
Modulation of stress- and cocaine prime-induced reinstatement of conditioned place preference after memory extinction through dopamine D3 receptor
(Elsevier, 2019-01-29) Guerrero-Bautista, Rocío; Hidalgo, Juana M.; Cárceles-Moreno⁠, Francisco José; Molina, Guillermo; Núñez, Cristina; Ribeiro do Couto, Bruno; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología; Anatomía Humana y Psicobiología
Open Access
Hypothalamic Crh/Avp, plasmatic glucose and lactate remain unchanged during habituation to forced exercise
(Frontiers, 2020-05-15) Toval, Angel; Vicente-Conesa, Francisco; Martinez-Ortega, Paloma; Kutsenko, Yevenhiy; Morales-Delgado, Nicanor; Garrigos, Daniel; Alonso Fuentes, Antonia; Ferrán Bertone, José Luis; Ribeiro do Couto, Bruno; Popovic Popovic, Miroljub; Anatomía Humana y Psicobiología
It has been demonstrated that physical activity contributes to a healthier life. However, there is a knowledge gap regarding the neural mechanisms producing these effects. One of the keystones to deal with this problem is to use training programs with equal loads of physical activity. However, irregular motor and stress responses have been found in murine exercise models. Habituation to forced exercise facilitates a complete response to a training program in all rodents, reaching the same load of physical activity among animals. Here, it was evaluated if glucose and lactate – which are stress biomarkers – are increased during the habituation to exercise. Sprague-Dawley rats received an 8-days habituation protocol with progressive increments of time and speed of running. Then, experimental and control (non-habituated) rats were subjected to an incremental test. Blood samples were obtained to determine plasmatic glucose and lactate levels before, immediately after and 30 min after each session of training. Crh and Avp mRNA expression was determined by two-step qPCR. Our results revealed that glucose and lactate levels are not increased during the habituation period and tend to decrease toward the end of the protocol. Also, Crh and Avp were not chronically activated by the habituation program. Lactate and glucose, determined after the incremental test, were higher in control rats without previous contact with the wheel, compared with habituated and wheel control rats. These results suggest that the implementation of an adaptive phase prior to forced exercise programs might avoid non-specific stress responses.
Open Access
Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories
(Frontiers Media, 2019-09-20) Gómez-Murcia, Victoria; Gómez-Fernández, Juan Carmelo; Almela, Pilar; Ribeiro do Couto, Bruno; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología
Morphine is thoroughly used for pain control; however, it has a high addictive potential. Opioid liposome formulations produce controlled drug release and have been thoroughly tested for pain treatment although their role in addiction is still unknown. This study investigated the effects of free morphine and morphine encapsulated in unilamellar and multilamellar liposomes on antinociception and on the expression and extinction of the positive and negative memories associated with environmental cues. The hot plate test was used to measure central pain. The rewarding effects of morphine were analyzed by the conditioned-place preference (CPP) test, and the aversive aspects of naloxone-precipitated morphine withdrawal were evaluated by the conditioned-place aversion (CPA) paradigm. Our results show that encapsulated morphine yields prolonged antinociceptive effects compared with the free form, and that CPP and CPA expression were similar in the free- or encapsulated-morphine groups. However, we demonstrate, for the first time, that morphine encapsulation reduces the duration of reward and aversive memories, suggesting that this technological process could transform morphine into a potentially less addictive drug. Morphine encapsulation in liposomes could represent a pharmacological approach for enhancing extinction, which might lead to effective clinical treatments in drug addiction with fewer side effects
Open Access
Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors
(Springer, 2021-01-04) Toval, Angel; Garrigos, Daniel; Kutsenko, Yevenhiy; Morales-Delgado, Nicanor; Tseng, Kuei I.; Ferrán Bertone, José Luis; Ribeiro do Couto, Bruno; Popovic Popovic, Miroljub; Anatomía Humana y Psicobiología
Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.