Ganaxolone is a new potencional antiepileptic drug, synthetic analog of allopregnanolone which is a metabolite of progesterone. Preclinical and clinical studies point out its anticonvulsive effect in the treatment of both partial and generalized seizures including refractory epilepsy. The aim of our research was to investigate changes in the motor performance of the immature rats after administration of ganaxolone. We also focused on the relation between motoric impairment and the age of the rats which correlates with the age of children. 90 immature rats of age 12, 18 and 25 days were tested. Rats were divided in three groups injected with doses of 20 mgGNX/kg or 40 mgGNX/kg and the control group. The tests for assessing motor performance were chosen with respect to the maturation of sensorimotor reflexes from the following batery of tests: righting test, bar holding test, wire mesh test, negative geotaxis test and open field test. There were no significant differences before and after injection of the drug and in comparison with the control group not even in comparison of classes of age. We have demonstrated that the dose of ganaxolone effective against epileptic seizures does not markedly affect the motoric performance of the immature rats. Powered by TCPDF (www.tcpdf.org)

La partie céphalique de notre corps est le siège de douleurs qui, comme la migraine, peuvent être très invalidantes. Le sous noyau caudal du trijumeau (Sp5C) assure le transfert des messages nociceptifs provenant de la face et des méninges vers les centres supérieurs. Ce transfert est modulé par des projections descendantes provenant de centres supraspinaux dont l'hypothalamus. Comment sont organisés les contrôles descendants hypothalamiques sur le Sp5C ? En utilisant le traceur retrograde, Fluorogold (FG), nous avons analysé les projections hypothalamiques sur le Sp5C. Elles proviennent du noyau paraventricular (PVN), de l'aire hypothalamique laterale (LH), de l'aire hypothalamique perifornicale (PFX), du noyau A11 et de l'aire retrochiasmatique (RCA). La zone ophtalmique V1 du Sp5C reçoit la plus forte densité de projections. Ces projections sont systématiquement bilatérales. Par double marquage immunohistochimique traceur/phénotype, nous avons précisé les phénotypes neurochimiques des neurones projetant du A11, LH et PFX vers le Sp5C. Dans le noyau A11, 60% environ de ces neurones sont dopaminergiques (DA) et 10% environ contiennent l'alpha-calcitonin gene related peptide (CGRP). De plus, 15% de ces neurones dans LH et 30% de ceux-ci dans PFX sont oréxinergiques. L'expression de Fos est augmentée dans le noyau A11 après stimulation nociceptive tonique inflammatoire (formol facial sous-cutané), indiquant que ce noyau contribue au traitement de l'information douloureuse. Cependant, ni les neurones DA ni les neurones FG expriment Fos. Par une approche comportementale et électrophysiologique, nous avons précisé le rôle des contrôles hypothalamiques dans la modulation de la nociception trigéminale. La lésion par acide kaïnique ou 6-OHDA d'un noyau A11 abaisse les réponses nociceptives comportementales (test au formol) chez le rat vigil. Pour tester l'hypothèse d'un contrôle hypothalamique orexinergique, nous avons enregistré les réponses électrophysiologiques de neurones trigéminaux à la stimulation électrique de leur champ récepteur. L'injection intracisternale (0.6 nmol dans 5μl) d'orexine A réduit (environ 50%) les réponses à l'activation sélectivement des fibres afférentes de type C sans modifier leur windup. Au total, plusieurs de nos résultats méritent d'être soulignés. (1) Les voies hypothalamiques descendantes semblent contrôler préférentiellement les inputs méningés. (2) Un dysfonctionnement prolongé du noyau A11 provoque un état d'hypoalgésie, suggérant que l'activation des afférences DA provoque un état d'hyperalgie. Or, les résultats d'injections locales de DA ou de manipulations aigues du noyau A11 suggèrent un contrôle DA inhibiteur sur l'information nociceptive. Le dysfonctionnement DA pourrait favoriser une plasticité dans le Sp5C. (3) Enfin, l'inhibition sélective des réponses C par l'orexine A, suggère l'existence d'un contrôle présynaptique inhibiteur du message nociceptif trigéminal. / Pain syndroms located in the head, such as migraine, can be particularly invalidating. Sensory inflow generated bynociceptors in the face and meninges activate neurons in the medullary dorsal horn (MDH), within the trigeminal system.There, a network of descending projections from cerebral structures enhance or inhibit the transfer of nociceptive informationto higher centers. However, the functional anatomy of such descending controls of nociceptive information are still ill-defined.Here, we investigated the descending hypothalamic projections to the MDH. Using the retrograde tracer, Fluorogold (FG), we analyzed the organization of hypothalamic projections to MDH. They originate from the paraventricular nucleus (PVN), lateral hypothalamic area (LH), perifornical hypothalamic area (PFX), A11 nucleus and retrochiasmatic area (RCA). Within MDH, the V1 area, where primary afferent fibers of the ophthalmic branch of the trigeminal nerve terminate, receives the strongest hypothalamic projections. Hypothalamic projections to MDH are bilateral. Using double-immunolabelling, we determined the molecular phenotype of A11 nucleus, LH and PFX projecting neurons to MDH. In A11 nucleus, about 60% of projecting neurons to MDH are dopaminergic (DA) and about 10% contain the alphacalcitonin gene related peptide (CGRP). Fifteen percent of LH projecting neurons to MDH and 30% of PFX ones contain orexin. Pain (facial formalin test) elevates Fos expression in A11 nucleus, suggesting that it contributes to pain processing. However, it is worth noting that Fos-immunoreactive neurons are neither DA nor projecting neurons. We combined behavioral and electrophysiological techniques to get further insights into the role of hypothalamic projections on trigeminal pain. Lesion of A11 nuclei, by locally injecting kainic acid or 6-OHDA, reduces spontaneous pain behavior (facial formalin test). To examine whether orexin descending hypothalamic projections control trigeminal pain, we examined the effect of intracisternally applied orexin A on electrophysiological responses of trigeminal neurons to electrical stimulation of their receptive field. Orexin A (0.6 nmol in 5μl) selectively reduces (about 50%) C-fiber-evoked responses but not the windup phenomenon. Several of these results are worth to note. (1) Descending hypothalamic projections predominantly control VI area of MDH, where primary afferent fibers innervating the meninges terminate. (2) The effect of long-lasting dysfunction of A11nucleus suggests that activation of descending DA projections produce a state of hyperalgesia. This is at odds with theconclusion of previous reports on the effects of local administration of DA or acute manipulations of A11 nuclei, suggestingthat descending DA projections rather inhibit nociceptive transmission. Long-lasting dysfunction of descending A11 DAprojections might enable plasticity changes in DH neuronal network. (3) That orexin A selectively inhibits C-fiber-evokedresponses suggests that orexin A selectively controls the transfer of nociceptive information via a presynaptic mechanism.

A dissertation submitted to the Faculty of Dentistry, University of the Witwatersrand, Johannesburg, in part- fulfilment of the requirements for the Degree of Master of Science in Dentistry 1982 / Rat embryos of the post-implantation stage are grown on a static culture medium, for the purpose of assessing growth and development over a 2 day period. The technique used is referred to as the petri-dish culture chamber method. This involves the culture of rat embryos on rat serum, in a controlled environment. Postimplantation embryos from the 6,5 to 8 day stage, and consisting simply of the 3 germ layers, showed a 60% survival rate in. vit/io after 2h hours and A8 hours respectively. After a full A8 hours in vitfio the embryos demonstrated well developed beating hearts, and a neural groove in the process of closing. The survival rate of embryos explanted at later stages was not as successful. The results compare favourably with the results of other workers, using the same method of culture. An advantage of the petri-dish culture chamber is that it allows for easy experimental access to the embryos at all times;a factor to be considered in any technique involving surgical intervention. Although more sophisticated methods have since superseded the static environment petri-dish technique, it is recommended here that this method should not be totally replaced by the more modern circulating culture medium technique. / IT2017

Thesis advisor: John P. Christianson / In social species, animals must detect, evaluate and respond to the states of other individuals in their group. A constellation of gestures, vocalizations, and chemosignals enable animals to convey affect and arousal to others in nuanced, multisensory ways. Observers integrate such social information with environmental cues and internal physiology to general social behavioral responses via a process called social decision-making. The mechanisms and anatomical correlates of social decision-making, particularly those that allow behavioral responses to others’ emotional states, are not fully known. Therefore, the objective of this dissertation is to broaden the anatomical understanding of social decision-making by investigating the role of the insular cortex in social behaviors that depend upon others’ emotional state. Using a novel behavioral paradigm, I present causal evidence that implicates the insular cortex and its projections to the nucleus accumbens in social affective behavior. These findings are consistent with evidence from the literature that suggests insular cortex is positioned to convey sensory cues to social brain structures to produce flexible and appropriate behavioral responses to social affective cues. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Thesis advisor: Jon C. Horvitz / Previous research has yielded conflicting results regarding the involvement of mesolimbic dopamine in Pavlovian and operant tasks. While there is abundant evidence that an operant lever press requires intact dopamine (DA) D1 transmission in the nucleus accumbens (ACB) and in the basolateral amygdala (BLA), there is conflicting evidence regarding the specific brain sites at which DA mediates a Pavlovian approach response. The present study was designed to compare the effects of ACB and BLA D1 receptor-blockade on an operant and Pavlovian task, while minimizing differences in behavioral response topography. Animals were trained on either a Pavlovian cued approach task or an operant cued nosepoke task. In the Pavlovian approach task, a tone signaled a pellet delivery to which animals responded with a head entry into a food compartment. In the operant nosepoke task, animals were trained to emit a nosepoke in response to the same tone, in order to trigger a pellet delivery. Bilateral microinfusions of the D1 antagonist SCH 23390 (0, 1 or 2 microgram/side) into either the ACB or the BLA produced a dose-dependent disruption of the operant nosepoke. In contrast, the Pavlovian cued approach response was unaffected by D1 antagonist microinfusions into either the ACB or the BLA. In addition, infusion of SCH 23390 into either site suppressed general locomotion. The results suggest a dissociation of the anatomical substrates mediating an operant nosepoke and a Pavlovian approach, despite similar response topographies. These findings are consistent with the notion that D1 activity at the ACB and BLA plays a role in the expression of operant responses, but not in the expression of Pavlovian approach responses. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Science, 2000.

Thesis advisor: John P. Christianson / Accurate discrimination between safety and danger is necessary for survival, but is aberrant in individuals with post-traumatic stress disorder (PTSD). Despite its clinical relevance, very little is known about the cognitive and neural processes that underlie safety learning. Understanding how cues become safety signals is critical to understanding the impairments in fear modulation observed in individuals with PTSD. PTSD is more prevalent in women than men, and while research on sex differences in safety learning is limited, there is substantial evidence that males and females acquire and utilize safety signals differently. The aim of this dissertation is to describe behavioral sex differences in learning and recall of fear discrimination and explore the neural circuitry that allows this discrimination to occur. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / No presente estudo foram utilizadas misturas de Ãleos em concentraÃÃes nutracÃuticas com razÃo de ω6:ω3 baixa que favorece uma aÃÃo antiinflamatÃria e a razÃo de ω9:ω6 alta com aÃÃo antioxidante. O objetivo do estudo foi estudar os efeitos das misturas de Ãleos de ω9, ω6 e ω3 na queimadura tÃrmica e avaliar se as fontes de ω3 (ALA, EPA ou DHA) interferem nos efeitos das misturas na queimadura. Foram utilizados 36 ratos Wistar, distribuÃdos em 6 grupos: Ãgua, queimado + Ãgua [Q + Ãgua], queimado + isolipÃdico [Q + Iso], queimado + mistura de Ãleos 1 [ALA], queimado + mistura de Ãleos 2 [ALA+EPA+DHA de peixe] e queimado + mistura de Ãleos ω3[ALA+DHA de algas marinhas] com seis animais em cada grupo. Realizada queimadura por conduÃÃo direta causando lesÃo de espessura total do dorso dos animais, em seguida admininstrada por via orogÃstrica as misturas de Ãleos por sete dias. Avaliada a lesÃo cutÃnea por macroscopia (planimetria digital), microscopia, imunohistoquimica (anti-Ki-67, anti-NFκB, anti-HSP 27 e anti-HNEJ) e painel de citocinas (IL-1, IL-6, IL-10, IL-18, TNF-alpha, INF-gama e CSF-GM). Na macroscopia os ratos que receberam a mistura 3 apresentaram menor Ãrea de lesÃo, assim como as misturas 1, 2 e isolipÃdica quando comparadas com a Ãgua. Na microscopia apenas os animais que receberam a mistura 3 (ALA+DHA de algas marinhas) apresentaram menor extensÃo da lesÃo em relaÃÃo a Ãgua. Ao avaliar o Ki-67 a mistura 3 induziu aumento da proliferaÃÃo celular em relaÃÃo aos demais grupos. Apenas a mistura 3 foi capaz de inibir NFκB. NÃo houve diferenÃa entre os grupos em relaÃÃo a HSP 27, HNEJ e painel de interleucina. A mistura de Ãleos ω3, na qual a fonte à ALA+DHA de algas marinhas, tem efeitos de: inibir o NFkB, aumentar a proliferaÃÃo celular, reduzir Ãrea de lesÃo e extensÃo da queimadura.

Release of glutamate in cerebral ischemia results in an excitotoxic reaction in the central nervous system resulting in neuronal cell loss. Providing neuronal protection via N‐methyl D‐asparate (NMDA) receptor blockade in response to cerebral ischemia may result in preservation of function following ischemia. The present study was designed to test compound AT010, an NMDA signaling antagonist, on behavioral compensation and infarct size in a cerebral ischemia model in the rat. Animals were surgically implanted with a filament via the external carotid artery, providing an occlusion of he medial cerebral artery for 60 min. Approximately 30‐45 minutes prior to surgery, the compound AT010 (3uM or 10uM) or saline was iv administered at 1% of body weight. All animals were behaviorally tested on behavioral tasks that analyzed postural reflex, limb placement, righting reflex, adhesive removal, and behavioral motor function at 3, 7, and 14 days post‐ischemia. In addition, animals were tested on the Morris water maze, a spatial memory task 28 days post‐ischemia. Regardless of dose, composite neurological scores for all motor and sensory tasks were higher for animals given AT010 compared to saline at 7 and 14 days post‐ ischemia. Water maze results revealed significant improvement of animals administered the higher dose of AT010 (10uM) on acquisition and probe trial performance, although no effect was revealed for the lower dose (3 uM). Finally, analysis of brain tissue samples revealed no significant effect on infarct size. These results indicate that compensation occurred throughout the undamaged brain areas, likely through synaptic communication changes as a result of drug treatment.

The purpose of this study was to explore the behavioral effects of amniotic fluid (AF) and milk in the newborn rat. Previous research has documented behavioral effects in the fetal and neonatal rat. For example, oral exposure to AF and milk reduces the response to chemosensory stimulation in rat fetuses (Korthank & Robinson, 1998) and newborns (Méndez-Gallardo & Robinson, 2010). In addition, some of the behavioral effects of AF and milk are mediated by the endogenous opioid system in the perinatal rat, including modulation of the facial wiping response (Korthank & Robinson, 1998; Méndez-Gallardo & Robinson, 2010), the stretch response induced by milk in the fetal rat (Smotherman & Robinson, 1992b), and the effect of milk as an unconditioned stimulus (US) during associative learning in the fetal rat (Robinson et al., 1993). Taking into account the literature that suggests similarities between AF and milk, this study aimed to evaluate whether transnatal continuity in the behavioral effects of AF and milk could be found and whether mediation by the endogenous opioid system is the underlying mechanism of these effects. To fulfill this purpose, overall behavioral activation, crawling locomotion, oral responses to an artificial nipple, and associative learning were investigated in the newborn rat. Results showed that, (a) oral exposure to AF resulted in higher levels of behavioral activation than oral exposure to milk, (b) exposure to the odor of AF or milk did not produce significant behavioral activation, although the odor of milk seemed to evoke higher levels of behavioral activity than exposure to the odor of AF, (c) both AF and milk odor elicited crawling locomotion, (d) odor of AF or milk did not promote oral grasping of an artificial nipple, but promoted mouthing responses and distinctive movements of the forepaws, (e) contingent presentations of an artificial nipple as the conditioned stimulus (CS), with AF or milk as the US, promoted mouthing responses during reexposure to the CS, but facial wiping after CS reexposure was not modified as a result of conditioning, and (f) mediation of the opioid system was evident only during hindlimb activity after oral exposure to AF or milk and during mouthing responses to the CS after associative learning. These findings suggest that oral exposure to AF or milk consistently evoke opioid responses in the neonatal rat, but exposure to the odor of AF or milk alone does not. Through postnatal testing and the direct comparison of the behavioral effects of AF (a feature of the prenatal environment) with milk (a feature of the postnatal environment), this study contributes to a better understanding of mechanisms that promote behavioral continuity before and after birth.