Liliana de Sousa

Transthyretin is involved in depression-like behaviour and exploratory activity

Transthyretin (TTR), the major transporter of thyroid hormones and vitamin A in cerebrospinal fluid (CSF), binds the Alzheimer β‐peptide and thus might confer protection against neurodegeneration. In addition, altered TTR levels have been described in the CSF of patients with psychiatric disorders, yet its function in the CNS is far from understood. To determine the role of TTR in behaviour we evaluated the performance of TTR‐null mice in standardized tasks described to assess depression, exploratory activity and anxiety. We show that the absence of TTR is associated with increased exploratory activity and reduced signs of depressive‐like behaviour. In order to investigate the mechanism underlying these alterations, we measured the levels of cathecolamines. We found that the levels of noradrenaline were significantly increased in the limbic forebrain of TTR‐null mice. This report represents the first clear indication that TTR plays a role in behaviour, probably by modulation of the noradrenergic system.

Can Dogs Prime Autistic Children for Therapy? Evidence from a Single Case Study

BACKGROUND AND OBJECTIVES Canine-assisted therapy has been receiving growing attention as a means of aiding children with autism spectrum disorder (ASD). Yet, only limited studies have been done and a great deal of literature related to this intervention is anecdotal. The present study aims at providing additional quantitative evidence on the potential of dogs to positively modulate the behavior of children with ASD. SETTINGS/LOCATION, SUBJECTS, AND INTERVENTIONS A 12-year-old boy diagnosed with ASD was exposed, at his usual treatment location (the Portuguese Association for Developmental Disorders and Autism at Vila Nova de Gaia, Portugal), to the following treatment conditions: (1) one-to-one structured activities with a therapist assisted by a certified therapy dog, and (2) one-to-one structured activities with the same therapist alone (as a control). To accurately assess differences in the behavior of the participant between these treatment conditions, the therapist followed a strict research protocol. The behavior of the participant was continuously video-recorded during both treatment conditions for further analysis and comparison. Treatment outcomes: In the presence of the dog, the participant exhibited more frequent and longer durations of positive behaviors (such as smiling and positive physical contacting) as well as less frequent and shorter durations of negative behaviors (such as aggressive manifestations). CONCLUSIONS These findings are in accordance with previous experimental work and provide additional support for the assertion that dogs can prime autistic children for therapy. Ultimately, this study may contribute toward a change for full acceptance of canine-assisted therapy programs within the medical milieu. Additional studies using a similar research protocol on more autistic children will certainly help professionals to work on the most effective methods to individually serve this population through canine-assisted interventions.

Auditory contagious yawning in domestic dogs (Canis familiaris): first evidence for social modulation

Dogs’ capacity to ‘catch’ human yawns has recently attracted the attention of researchers in the field of animal cognition. Following recent studies suggesting that contagion yawning in humans, and some other primates, is empathy-related, some authors have considered the possibility that the same mechanism may underlie contagious yawning in dogs. To date, however, no positive evidence has been found, and more parsimonious hypotheses have been put forward. The present study explored the ‘contagion-only’ hypothesis by testing whether the mere sound of a human yawn can be sufficient to elicit yawning in dogs, in a way that is unaffected by social–emotional factors. Unexpectedly, results showed an interesting interplay between contagion and social effects. Not only were dogs found to catch human yawns, but they were also found to yawn more at familiar than unfamiliar yawns. Although not allowing for conclusive inferences about the mechanisms underlying contagious yawning in dogs, this study provides first data that renders plausible empathy-based, emotionally connected, contagious yawning in these animals.

The Role of Expressed Emotion, Self-Concept, Coping, and Depression in Parasuicidal Behavior: A Follow-up Study

The objective of this study was to characterize Expressed Emotion in families of individuals with parasuicidal behavior, a non-fatal act in which there is self-harm or deliberate excessive ingestion of a substance and to examine the significant relationships between Expressed Emotion (EE), Coping, Depression, Self-concept, and parasuicidal behaviors. The sample consisted of 67 subjects divided into two groups. The first group was made up of 34 parasuicides. Parasuicidal behavior, self-concept, coping, depression and the familys EE were assessed in this group. The control group was composed of 33 young people with identical characteristics (age: 15–24; gender: more female; and residence). All the subjects were followed up for a 9 month period, during which time EE and recurrent parasuicidal behaviors were assessed. Parasuicides showed significant differences (at a 0.05% significance level) in comparison to the control group They showed more Depressed, less Coping, and less Self-concept. There was also an intimate family atmosphere with a high EE. The parasuicides whose families had a high EE showed more recurrent parasuicidal behaviors. The results demonstrate that EE is a predictor of recurrent parasuicidal behaviors and that its assessment in families of young parasuicides is useful.

Effects of Postnatal Cocaine Exposure and Environmental Enrichment on Rat Behavior in a Forced Swim Test

Abstract: This study examined the effects of environmental enrichment on rats exposed to cocaine during the first month of life, in several categories of behavior observed in a forced swim test. Wistar rats were divided in four groups. The first included pups that were subjected to injections of cocaine hydrochloride (15 mg/kg body weight/day, subcutaneously, in two daily doses, from postnatal days 1 to 27) and reared in an enriched environment (CocEE); the second, pups that were subjected to injections of cocaine (as previously described) and reared in a standard environment (CocSE); the third, pups that were subjected to saline injections and reared in an enriched environment (SalEE); the fourth, pups that were subjected to saline injections and reared in a standard environment (SalSE). On postnatal days 26 and 27, rats were tested in a swimming pool in two 5‐min sessions. The categories of behavior studied in this work were: fast swim, slow swim, struggling, diving, and immobility. Results showed that postnatal cocaine exposure decreased the time spent on fast swim during the two sessions and increased the immobility behavior during the second session in CocSE pups compared with SalSE pups. SalEE pups increased the time spent in fast swim, slow swim, and diving, and decreased the time spent in struggling and immobility during the two sessions compared with SalSE pups. CocEE animals spent more time in fast swim and struggling and less the time in immobility compared with CocSE pups. The present results suggest that postnatal cocaine exposure affects the ability of these animals to cope with stressful situations, and that environmental enrichment seems to enable the rats to adopt a more active strategy, one that allows them to better cope with this particular stress situation.

Hormonal, neurochemical, and behavioral response to a forced swim test in adolescent rats throughout cocaine withdrawal.

The use of cocaine in adults has been linked to depression and/or anxiety. Several studies have shown an association between cocaine‐primed craving and depressive symptoms. In animal models, the forced swim test (FST) is frequently used for screening depressive‐like behavior. This study aimed to verify the presence of depression‐like symptoms in adolescent rats after chronic cocaine exposure by analyzing behavior in a FST. The subsequent alterations in neurotransmitters and hypothalamus‐pituitary‐adrenal axis activity induced by this test were also analyzed. Both male and female adolescent Wistar rats were submitted to a chronic “binge” pattern of administration of cocaine hydrochloride, and subjects were tested in a forced swim test 2 days after cocaines last administration. At the end of the behavioral test, trunk blood was collected for quantification of corticosterone plasma levels, and hypothalamus, prefrontal cortex, amygdala, and hippocampus were dissected for neurochemical determinations. No significant differences were found in the behavior on the FST of both males and females after withdrawal from chronic cocaine administration. Nevertheless, plasma levels of corticosterone were increased in cocaine‐treated males, although not significantly (P= 0.065). In females cocaine failed to affect corticosterone levels. Of interest, neurochemical analyses showed that dopamine turnover was decreased in amygdala in cocaine‐treated males (not significantly, P= 0.055). No significant differences were found on neurotransmitter levels in the other brain regions analyzed. Withdrawal from chronic cocaine administration during adolescence did not have a significant effect on stress‐induced behavioral alterations, although the neurochemical response to the stressful situation provided by FTS seemed to be affected.

Postnatal exposure to cocaine in rats housed in an enriched environment: effects on social interactions

This study was undertaken to evaluate the effects of environmental enrichment (EE) in rats exposed to cocaine during the first month of postnatal life by examining several categories of social behaviour (play fighting, social investigation, comfort behaviours and invitation to play). Wistar rats were divided in four groups: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day), sc, in two daily doses, from postnatal day (PND) 1 to 28 and reared in EE; exposed to cocaine as previously described and reared in standard environment (SE); saline-exposed and reared in EE; pups saline-exposed and reared in SE. On PND 21, 24 and 28, social interactions were examined for 10 min. Results show that cocaine animals reared in SE decreased the frequency of play solicitation. Control animals reared in EE exhibited decreased play fighting and social investigation behaviours compared to SE-reared rats. Animals postnatally exposed to cocaine when reared in EE displayed more comfort and invitation to play behaviours and decreased social investigation compared with SE-reared animals. The results suggest that in rats postnatally exposed to cocaine, EE rearing elicited differences in both processing of environmental stimuli and a response to social challenges. Human & Experimental Toxicology (2007) 26, 303-309

Neonatal exposure to cocaine: altered dopamine levels in the amygdala and behavioral outcomes in the developing rat.

Abstract: The amygdala is a brain region that is known to be implicated in the development of behavioral sensitization to cocaine. This area is often related to conditioned associations, stress responses, and anxiety; and these behaviors are usually posited to be due to altered dopamine levels. This study aimed to evaluate the effects of neonatal exposure to cocaine on the levels of neurotransmitters in the amygdala of developing rats and to relate these levels with open‐field observations, mainly rearing behavior, that is regarded to reflect emotional components. Male and female Wistar rats were given 15 mg of cocaine hydrochloride/kg body weight, subcutaneously, in two daily doses, from postnatal day 1 (PND1) to PND30. Controls were given 0.9% saline. Open‐field activity was registered on PND14, 21, and 30 in three sessions of 15 min each. In PND30, rats were decapitated, and the amygdala dissected from both brain hemispheres and processed for determination of dopamine (DA) and metabolites by high‐performance liquid chromatography with electrochemical detection (HPLC‐EC). Results show that in PND14 and 21 all registered activity behaviors were increased in male and female cocaine‐exposed animals. In PND30, there was a significant decrease in rearing and in global activity in the group exposed to cocaine, and DA levels were significantly decreased in the amygdala of the same group. No differences were found between the left and right amygdala. These results suggest that chronic neonatal cocaine administration leads to depletion of DA levels in the amygdala, which is consistent with previous findings. Furthermore, the lower levels of DA are associated with decreased rearing behavior, which may indicate emotional depression. These results can help to clarify the role of amygdala in cocaine‐induced behavioral sensitization in the developing rat.

Postnatal cocaine exposure: effects on behavior of rats in forced swim test.

Abstract: Exposure to cocaine in early periods of postnatal life has adverse effects on behavior, namely, it induces the display of anxiety and fear‐like behaviors that are associated with stress and depression. This study examined the effects of early developmental cocaine exposure in several categories of behavior observed in forced swim test. Male and female Wistar rats were given 15 mg/kg of cocaine hydrochloride/body weight/day, subcutaneously, in two daily doses, from postnatal day (PND) 1 to PND27. Controls were saline injected in the same protocol. In PND26‐PND27, rats were placed in a swimming pool during 5 min in two sessions. The categories of behavior studied in this work included horizontal and vertical rotation, vibrissae clean, head clean, fast and slow swim, struggling, floating, sliding, diving, head‐diving, and wagging head. Results showed differences in the frequencies of several behavioral categories that allowed the discrimination of the behaviors that may constitute “behavioral despair” indicators, as well as which behaviors are most affected by cocaine exposure. Cocaine groups were less active and more immobile than controls. These results suggest that postnatal exposure to cocaine can produce depression‐like effects and affect the ability of these animals to cope with stress situations.

Prenatal Exposure to Cocaine and Enriched Environment

Abstract:  Exposure to cocaine throughout gestation may produce several deleterious outcomes in the offspring that include effects on neurotransmitter systems and structure of the central nervous system. Such changes are most likely correlated with behavioral alterations. Environmental enrichment (EE) in early stages is a factor that affects structural and behavioral development. This article examines the effects, upon social interactions, of EE during the first month of life in rats prenatally exposed to cocaine. Wistar dams were subcutaneously exposed to 60 mg/kg of cocaine divided in two daily doses from gestational day (GD)8 to GD22. Pair‐fed controls were given saline vehicle in the same protocol. Offspring were distributed to the different environments in four experimental groups. Group 1: offspring from dams prenatally exposed to cocaine as previously described and reared in EE from postnatal day (PND)1 to PND28; Group 2: pups from cocaine‐exposed dams and reared in a standard environment (SE); Group 3: pups from pair‐fed saline‐exposed dams and reared in EE; Group 4: offspring from saline‐exposed dams and reared in SE. On PND21, 24, and 28, rats were examined in several social behavioral categories (play fighting, social investigation, comfort behaviors, and solicitation to play) for 10 min. Animals reared in SE do not display any differences due to treatment in the behavioral categories analyzed. Control offspring reared in EE presented decreased play fighting, decreased solicitation to play, and decreased social investigation compared to the control SE group, while cocaine‐exposed animals reared in EE did not present these variations. These results suggest that EE rearing may unmask hidden effects of prenatal cocaine exposure.