Genes and environment interact to determine an individual’s vulnerability or resilience to several psychiatric disorders, including alcohol use disorder (AUD). Alcohol use is often initiated during adolescence and early onset drinking is associated with increased risk for later AUD. Childhood and adolescence are periods of extensive brain maturation, which makes young individuals more susceptible to environmental influence. However, little is known about early environmental influence on reward pathways and behaviors involved in the development of AUD. Changes in the endogenous opioid and dopamine systems, as well as individual differences in risk behaviors are all believed to play important roles in the increased vulnerability seen after adverse early life events and early onset drinking. The overall aim of the thesis was therefore to investigate the influence of early environmental factors on adolescent alcohol intake, endogenous opioids, dopamine dynamics and alcohol-induced effects in rats to increase our knowledge of neurobiological factors underlying vulnerability to AUD. Furthermore, individual behavioral differences and their correlation to basal and drug-induced neurobiological responses in rats were also investigated. Animal models of different early environments, e.g. maternal separation and social vs. single housing, and adolescent alcohol consumption have been used to study effects on behavior, endogenous opioid peptides and dopamine dynamics. The results identified the amygdala and dorsal striatum as interesting brain regions in which endogenous opioids and dopamine, respectively, are impacted by early environmental factors. The amygdala and the dorsal striatum are both hypothesized to be involved in the shift from initial drug use to compulsive use and changes in these areas may be underlying environmentally increased vulnerability to AUD. Furthermore, behavioral phenotypes in relation to individual neurobiological responses were identified. High risk-taking behavior was associated with a more pronounced response to amphetamine, but the inherent dopamine response was instead associated with risk-assessment behavior. In conclusion, several brain regions of interest for future research were identified. Furthermore, the results contribute to increased understanding of factors involved in the development of vulnerability for AUD in adolescents and young adults.

Apresentamos dados e argumentos que indicam que: a) as crises epilépticas apresentadas por Trinomys yonenagae em campo e em cativeiro são espontâneas e idiopáticas; e b) elas podem ser decorrentes de processos evolutivos. A epilepsia nesta espécie foi caracterizada em cativeiro a partir de um cadastro iniciado há 16 anos, formado por progenitores e descendentes de seis colônias de T. yonenagae, coletados na Caatinga de Ibiraba (BA), e adultos (129,90 ± 5,92g) e filhotes nascidos em cativeiro num total de 295 indivíduos. A prevalência e a incidência em indivíduos epilépticos (EE) foram estimadas e as crises epilépticas foram analisadas por meio das manifestações comportamentais, baseando-se na escala de Racine. Aspectos da procriação (n=11), a locomoção, a ansiedade (testes de arena, n= 35) e índices fisiológicos (balanço hídrico-alimentar, n=6), importantes ao fitness, foram mensurados. Somente duas colônias apresentaram EE representando 9% e 28% dos nascimentos. Do total de indivíduos (165 e 130) 9,8% são EE (n=29; 14 e 15), sendo que as representam 52% e os 48%. A prevalência é de 20 a 30% e a incidência variou de 2 a 10 casos/ano, nos últimos cinco anos. As crises são observadas somente em adultos (n=24) a menor latência é de 13m e a frequência é variável (1 a 24 em seis anos). A maioria iniciou-se por congelamento e 50% atingiram o estágio 5 da escala de Racine. Em todos os casais, de 5 a 50% dos filhotes são EE e ocorreu estro pós-parto, como esperado para a espécie. Os filhotes são saudáveis e tanto a média de filhotes por ninhada (1,9±0,3), como a média do número de ninhadas por casal (6,5±5,0) é igual à de casais não epilépticos (NE). O teste de arena indica que descendentes de EE (DE) e as EE são menos ansiosas que as NE. Não há diferença entre os grupos dos índices fisiológicos estimados. A diferença no número de EE nas colônias, a alta prevalência e % de filhotes EE, e a diferença de comportamento das fêmeas DE indicam a base genética desta epilepsia. Neste contexto, consideramos que em Trinomys yonenagae, a epilepsia límbica não compromete o fitness, o que abre possibilidades de ser decorrente de processos evolutivos envolvendo o escalonamento de respostas de anti-predação / We present data and discuss the possibility that: a) the seizures presented by Trinomys yonenagae in the wild and in captivity are spontaneous and idiopathic, and b) they may be due to evolutionary processes. Epilepsy was characterized in this species in captivity from a survey started 16 years ago, made up of parents and descendants from six colonies of T. yonenagae collected in the Caatinga of Ibiraba (BA), and adults (129.90 ± 5.92 g) and pups born in captivity in a total of 295 individuals. The prevalence and incidence in individuals with epilepsy (EE) were estimated and seizures were analyzed by behavioral manifestations, based on Racine´s scale. Locomotion and anxiety indexes (open-field test, n = 35), as well as aspects of breeding (n = 11) and physiological indicators (balance food and water, n = 6), important to fitness were measured. Only two colonies showed EE, representing 9% and 28% of births. Approximately 10% of total individuals (165 and 130 ) are EE (n = 29, 14 and 15 ), and the represent 52 and 48%. In the last five years prevalence is 20-30%, and incidence ranged from 2 to 10 cases/ year. Seizures are only observed in adults (n = 24), the lowest latency is 13 months and the frequency is variable (1 to 24 in six years). The first stage is freezing and 50% reached stage 5 of Racine´s scale. In all couples, 5-50% of puppies are EE and occurred postpartum estrus, as expected for the species. The puppies are healthy and both the average offspring per litter (1.9 ± 0.3), as well as the average number of litters per couple (6.5 ± 5.0) is equal to values presented by non-epileptic couples (NE). The open-field test indicates that descendants of EE (DE) and EE are less anxious than NE. There is no difference between EE and NE regarding food and water intake. The difference in the number of EE in the colonies, the high percentage of EE pups, and the difference in the behavior of DE indicate the genetic basis of this epilepsy. In this context, we consider that in Trinomys yonenagae the limbic epilepsy seems to not compromise the fitness, which opens possibilities to be the result of evolutionary processes involving the escalation of antipredator responses

O uso de répteis como modelos experimentais é limitado, principalmente devido às particularidades fisiológicas da classe, como as oscilações diárias e sazonais em seu comportamento. O objetivo deste estudo foi avaliar a atividade locomotora e nociceptiva de teiús (Salvator merianae) e iguanas-verdes (Iguana iguana) submetidos a testes comportamentais, ao longo do dia e do ano. Foram utilizados seis exemplares de cada espécie, mantidos em sala com temperatura ambiental (24 a 30°C) e fotoperíodo (12h:12h) controlados. Esses foram avaliados ao longo do dia (0:00h, 6:00h, 12:00h, 18:00h) e ao longo do ano (análise mensal). A análise locomotora foi realizada através do teste de campo aberto (teiús e iguanas), no qual o animal foi colocado no centro de uma arena circular por 15 minutos, e recebeu um ponto por cada ultrapassagem pelas subdivisões da mesma; e pelo teste de natação forçada (iguanas), no qual o tempo de atividade foi mensurado em piscina sem saída por 2 minutos. A resposta nociceptiva foi avaliada por meio de mensuração do período de latência do membro em resposta a estímulo nocivo térmico (25 segundos; 245 ± 7 mW/cm2) na superfície plantar do membro do animal. Não foram detectadas oscilações ao longo do ano no teste de campo aberto em nenhuma das espécies. Ao longo do dia, oscilações foram detectadas de Fevereiro a Dezembro em teiús; e em Abril, Maio, Junho e Outubro em iguanas. O tempo de atividade das iguanas foi menor em Janeiro e às 0:00h. Maiores latências de retirada do membro foram observadas nos meses de Maio e Agosto e às 6:00h em ambas espécies. Conclue-se que teiús e iguanas-verdes em ambiente controlado apresentam oscilações significativas em comportamento observado em teste de campo aberto, teste de natação forçada (somente iguanas) e teste plantar, que aparentemente não seguem padrões anuais claros, sendo provavelmente influenciado por fatores múltiplos ainda não compreendidos para as espécies. / The use of reptiles as experimental models is limited due to their physiological particularities, such as daily and annual fluctuations in behavior. The aim of this study was to evaluate locomotor and nociceptive activities of tegus (Salvator merianae) and green iguanas (Iguana iguana) throughout the day and the year, when undergoing behavioral tests. Six animals from each species, kept under controlled room temperature (24 to 30°C) and photoperiod (12h:12h), were used. They were evaluated throughout the day (0:00h, 6:00h, 12:00h and 18:00) and the year (monthly). Locomotor activity was measured by the open field test, in which the animal was placed in the center of a round arena for 15 minutes and the number of crossings through the subdivisions of the arena was counted, and by the forced swim test (iguanas), in which the activity period was timed after animals were placed in a pool with no scape for 2 minutes. Nociceptive activity was measured as the latency to limb withdrawal reflex in response to a noxious thermal stimulus (25 seconds, 245 ± 7 mW/cm2) in the plantar surface of the animal\'s limb. No differences were detected in locomotor activity in the open field test throughout the year in both species. Throughout the day, fluctuations were detected from February to December in tegus, and in April, May, June and October in iguanas. Activity period in iguanas were shorter in January and at 0:00h. Longer latencies to withdrawal reflex were detected in May and August and at 6:00h in both species. In conclusion, tegus and green iguanas kept in controlled environment have fluctuations in behavior presented in the open field test, the forced swim (only iguanas) test and the plantar test, which apparently do not follow a clear seasonal pattern and are probably influenced by multiple factors that are still unknown for both species.

Le parasitisme est omniprésent dans l’environnement et une attention croissante est récemment apportée sur son impact sur les communautés écologiques. En effet, les parasites peuvent affecter la valeur adaptative des animaux sauvages, en altérant leur physiologie et/ou leur comportement. Ainsi, le rôle des parasites dans le maintien ou l’érosion des différences persistantes comportementales et cognitives entre individus est le sujet de nombreux débats et recherches. La relation entre l’infection parasitaire et le comportement de l’hôte est souvent complexe. Le comportement des individus agit sur leur susceptibilité au parasitisme, mais l’infection parasitaire peut aussi modifier le comportement de l’hôte, favorisant parfois la transmission du parasite. En outre, l’inclusion d’un proxy de santé, tel que la condition corporelle est importante à considérer dans des populations naturellement infectées où la santé des individus peut varier. Dans cette étude, nous avons examiné la relation entre un gradient de densité parasitaire, la personnalité (exploration et témérité), la cognition (apprentissage par stimuli aversifs) et la condition corporelle (Indice K de Fulton) chez les crapets-soleil (Lepomis gibbosus) sauvages, naturellement infectés par des endoparasites, comme le trématode responsable de la maladie du point noir (Trematoda : Apophallus sp. et Uvulifer sp.) et le ver solitaire de l’achigan (Cestoda : Proteocephallus ambloplites). Nous avons trouvé que l’exploration, mais pas la témérité, était répétable ce qui suggère que ce trait reflète la personnalité. De plus, l’exploration a diminué avec l’augmentation de la densité de parasites et la diminution de la condition corporelle de l’hôte. Ainsi, étant donné que la relation entre le comportement explorateur et la densité de parasites variait avec la condition corporelle, il est possible que les parasites aient un effet indirect sur le comportement de l’hôte en impactant sa physiologie. L’exploration variait également selon la densité de points noirs et la densité de cestodes, suggérant un potentiel conflit entre ces deux parasites, leurs hôtes finaux étant différents. Les individus avec plus de cestodes ont moins bien exécuté la tâche d’apprentissage, ce qui laisse à penser que ces parasites imposeraient un coût énergétique qui réduit les performances cognitives de l’hôte. Nos résultats contribuent à démontrer que les parasites et la condition corporelle de l’hôte doivent être pris en considération dans les études écologiques, comportementales ou physiologiques afin de mieux comprendre le maintien des variations inter-individuelles au sein des populations sauvages. / Parasites are ubiquitous in nature and increasing attention is given to their impact on ecological communities. Indeed, parasites can affect host fitness through changes in physiology and/or behaviour. Thus, their role in maintaining or eroding persistent inter-individual differences in behaviour (i.e. personality) and cognitive abilities in hosts is the subject of increasing study and debate. The relationship between parasite infection and host behaviour can sometimes be complex. For instance, personality traits may affect an individuals’ susceptibility to parasites. Conversely, parasite infection can itself modify host behaviour, sometimes favouring the parasite’s own transmission. In addition, including a general fitness proxy, such as body condition, is important when studying naturally infected populations, where individual health can vary greatly among individuals. Here, we examine the relationships among host body condition (Fulton’s K index), personality (i.e. exploration, boldness), cognition (aversive learning) and parasite density in wild pumpkinseed sunfish (Lepomis gibbosus), naturally infected with endoparasites, including trematodes causing blackspot disease (Trematoda: Apophallus sp. and Uvulifer sp.) and bass tapeworms (Cestoda: Proteocephallus ambloplites). We found that exploration but not boldness was repeatable, which suggests that this trait reflects personality. Host exploration decreased with both increasing parasite density and decreasing host body condition. Because the relationship between exploration and parasite density varied with body condition, this suggests a possible indirect effect of parasites on host behaviour through effects on host physiology. Exploration varied depending on blackspot and bass tapeworm density suggesting a possible conflict between these two parasites, as their final hosts are different. Inhibitory avoidance learning decreased with increasing cestode density, suggesting that these parasites could impose an energetic cost which decreases host cognitive performances. Our results provide more evidence that including host body condition and parasite density in ecological, behavioural or physiological studies can help better understand the persistence of inter-individual differences in wild populations.

Le parasitisme est de plus en plus considéré comme un facteur écologique pouvant créer des variations dans le comportement des individus. Toutefois, la direction de causalité entre le comportement et le parasitisme reste incertaine. Les infections expérimentales sont le plus souvent réalisées en laboratoire, limitant les inférences écologiques. À l’aide d’une infection expérimentale semi-naturelle, nous avons infecté avec succès des crapets-soleils (Lepomis gibbosus) dans un lac où ils ont été exposés à une variété de vers parasites (trématodes, cestodes), permettant d’examiner les effets de la co-infection naturelle chez les hôtes. Nous avons mesuré la témérité, l’exploration et l’activité avant et après l’infection expérimentale. En utilisant une approche bayésienne, nous avons trouvé que les traits de comportement initiaux exercent une forte influence sur la susceptibilité à l’infection : les poissons les plus téméraires et/ou les moins actifs au départ ont acquis une plus grande densité de points noirs (c.-à-d. points noirs visibles sous la peau, les nageoires et dans les muscles du poisson) et de cestodes lors de l’infection. Par ailleurs, nous avons montré que la condition corporelle est réduite par la densité de cestodes, suggérant la débilitation de l’hôte. La condition corporelle était corrélée positivement avec la distance parcourue, quel que soit le statut d’infection individuel. Nous avons également trouvé une relation négative entre la distance parcourue après l’infection et la densité de trématodes, suggérant que l’infection causant la maladie des points noirs diminue le niveau d’activité des hôtes. La témérité et l'exploration n'étaient pas affectées par la densité parasitaire ou la condition corporelle. Nous suggérons que la diminution de l’activité est causée par une réponse adaptative de l’hôte, visant à rediriger son énergie pour combattre l’infection. Sachant que les points noirs ont un cycle de vie complexe et que le crapet-soleil est un hôte intermédiaire, ce changement dans le comportement de l’hôte pourrait aider le parasite à compléter sa transmission aux oiseaux-hôtes piscivores en augmentant la prédation sur les poissons infectés. Bien que nous ne puissions confirmer la direction de causalité, nos résultats montrent qu’il existe un lien étroit entre le comportement et le parasitisme. Nous suggérons que deux mécanismes peuvent simultanément agir : le comportement initial des individus influence le risque d’infection, et l’infection peut créer de la variation au niveau de la plasticité comportementale des individus. / Parasitism is increasingly seen as an ecological factor that can create variations in individual behaviour. However, the direction of causality between behaviour and parasitism remains uncertain. Experimental infections are most often conducted in laboratories, limiting ecological inferences. Using a semi-natural experimental infection, we successfully infected pumpkinseed sunfish (Lepomis gibbosus) in a lake where they were exposed to various parasitic worms (trematodes, cestodes), allowing us to examine the effects of natural co-infection in hosts. We measured boldness, exploration, and activity before and after the experimental infection. Using a Bayesian approach, we found that initial behavioural traits strongly influence infection susceptibility: initially bolder and/or less active fish acquired a higher density of black spots (i.e., visible black spots under the skin, fins, and in the fish's muscles) and cestodes during the infection. Additionally, we found that body condition was reduced by cestode density, suggesting host debilitation. Body condition was positively correlated with distance swam, regardless of individual infection status. We also found a negative relationship between distance swam after infection and trematode density, suggesting that infection causing black spot disease decreases host activity levels. Boldness and exploration were not affected by parasite density or body condition. We suggest that a decrease in activity is caused by an adaptive host response to redirect its energy to combat the infection. However, since trematode parasites have a complex life cycle and pumpkinseed sunfish are intermediate hosts, decreases in activity levels following infection may make infected fish more susceptible to predation by piscivorous birds, which is needed for trematodes to complete their life cycles. While we cannot confirm the direction of causality, our results show a close link between behaviour and parasitism. We propose that two mechanisms may simultaneously operate: the initial behaviour of individuals influences their risk of infection, and infection can create variation in behavioural plasticity of individuals.