Papers by Francesca Damato
Methods in Molecular Biology, 2020
The evaluation of ultrasonic vocalizations (USVs) during isolation in 6-8-day-old mouse pups can ... more The evaluation of ultrasonic vocalizations (USVs) during isolation in 6-8-day-old mouse pups can give an indication of the perception of pups' discomfort and need for caretaker presence to overcome the unpleasant condition. Time spent vocalizing changed according to opioid activation, stress exposure, and genetic profile of pups. Deficits in attachment suggest altered opioid functioning and predisposal for long-term defective social behaviors and reward processes.
Behavioral and Neural Biology, 1987
Methods in molecular biology (Clifton, N.J.), 2015
The experimental approach to carry out a behavioral study involving opioids in mouse pups needs e... more The experimental approach to carry out a behavioral study involving opioids in mouse pups needs equipments and procedures different from those used for adult animals. Pups are immature at birth and only slowly acquire all the potentialities that characterize adult con-specifics. The standard and abnormal development of behavioral systems and their neural correlates can be followed during the first postnatal weeks, using appropriate methodologies that exploit characteristic pups' capabilities. Behavioral tests designed for pups to evaluate the activity and involvement of the opioid system, according to the well-known role of the system in adult animals, are described in this chapter.
Hormones and Behavior, 1992
Hypothalamo-pituitary-adrenocortical (HPA) response to a mild stressful procedure was investigate... more Hypothalamo-pituitary-adrenocortical (HPA) response to a mild stressful procedure was investigated in mice at Days 8, 10, 12, and 14 of postnatal development. Pups that were removed from the dam and exposed to a novel odor (clean bedding) for 15 min showed higher plasma corticosterone levels than pups whose mother was removed from the cage for 15 min or unhandled pups at all ages, although statistically significant differences were only evident at Days 12 and 14. Lower HPA axis responding in younger mice was not due to immaturity since 8-day-old mice showed a significant and larger increase of plasma corticosterone levels when separated from the mother and isolated from littermates in the absence of bedding. Mice daily exposed to clean bedding (15 min) for the first 13 days of life did not show reduced plasma corticosterone response when reexposed to the stressor at 14 days of age. Conversely, increased plasma corticosterone levels in dams in response to removal of pups was not detectable after repeated exposure to this manipulation (14 days) regardless of the procedure their pups were submitted to, thus ruling out a role of maternal corticosterone passing through the milk on which the pups were fed. These results demonstrate that 15 min exposure to clean bedding is a noninvasive procedure able to elicit HPA axis response in developing mice over a wide age range without producing habituation.
Behavioural Processes, 1986
D'Amato, F.R., 198. Time budgets and behavioural synchronization in aggregated and isolated male ... more D'Amato, F.R., 198. Time budgets and behavioural synchronization in aggregated and isolated male and female mice. Behav. Processes, 13: 385-397. Albino mice (Mus musculus), initially housed in single sex groups and, subsequently, in social isolation, were used in this study to analyze the influence of social companions on the amount and on the distribution throughout the day of several behaviours. An observational recording technique was employed to record behaviour during the dark phase of the day. Behavioural sex differences in grouped mice were observed in four out of six behavioural categories. Females generally proved to be more active than males. Furthermore, prolonged social housing conditions resulted in an increase in male social interactions, in concomitance with changes in their time budgets. Conversely, females showed a decrease over time in social interactions with only slight effects on their time budget. Isolation seemed to increase slightly both male and female activity levels. Subjects housed together generally showed significantly similar Rest, Feed and General Activity patterns throughout the dark phase of the day. By contrast, the averaged patterns of different groups generally proved to be dissimilar in grouped females, but not in grouped males. When isolated, mice showed a distribution of their activities throughout the day different from what they had displayed under social conditions. These data indicate that social environment has an effect on the individual activity profiles which results in a definite synchronization within female groups and in a tendency towards desynchronization within male groups.
Aggressive Behavior, 1987
Behavioural Brain Research, 2013
Autism is a pervasive disorder characterized by a complex symptomatology, based principally on so... more Autism is a pervasive disorder characterized by a complex symptomatology, based principally on social dysfunction. The disorder has a highly complex, largely genetic etiology, involving an impressive variety of genes, the precise contributions of which still remain to be determined. For this reason, a reductionist approach to the study of autism has been proposed, employing monogenic animal models of social dysfunction, either by targeting a candidate gene, or by mimicking a single-gene disorder characterized by autistic symptoms. In the present review, we discuss this monogenic approach by comparing examples of each strategy: the mu opioid receptor knock-out (KO) mouse line, which targets the opioid system (known to be involved in the control of social behaviors); and the Fmr1-KO mouse, a model for Fragile X syndrome (a neurodevelopmental syndrome that includes autistic symptoms). The autistic-relevant behavioral phenotypes of the mu-opioid and Fmr1-KO mouse lines are described here, summarizing previous work by our research group and others, but also providing novel experimental evidence. Relevant factors influencing the validity of the two models, such as sex differences and age at testing, are also addressed, permitting an extensive evaluation of the advantages and limits of monogenic mouse models for autism.
Behavioral and Neural Biology, 1993
Pharmacology Biochemistry and Behavior, 2007
Stressful events during certain neonatal periods may increase the vulnerability of an individual ... more Stressful events during certain neonatal periods may increase the vulnerability of an individual to develop psychopathology and/or drug dependence later in life. Therefore, in the present study, we assessed activity levels, emotionality, sensitivity to the effects of morphine, as well as expression of proenkephalin and prodynorphin in several brain regions in 35 and 90-day-old male mice, subjected to postnatal manipulation consisting in brief exposures to clean bedding (CB). In comparison with controls, CB mice showed reduced emotionality expressed as percentage of time in open arms of the elevated plus maze both at 35 days of life and in adulthood. Increased nociceptive threshold was also present in both time points measured. Conversely, higher locomotor activity was recorded in 35 days of life but not in adulthood. Analysis of film autoradiograms revealed no changes in prodynorphin mRNA level, but statistically significant decrease in the level of proenkephalin mRNA in striatum in young CB mice in comparison with young controls; no difference was observed between adult CB and control animals. CB adult mice also showed hypersensitivity to the rewarding effect of morphine in comparison with controls in the place preference test. In conclusion, our results revealed that in the critical period of development the effects of manipulation were evident, not only on behavioral responses but also on the neurochemical markers considered in the present research. Postnatal manipulation could induce changes in the dynamic neuronal processes occurring during development with long-term behavioral effects.
Pharmacology Biochemistry and Behavior, 1992
Dominant and subordinate male mice behave differently when exposed to a female, with subordinates... more Dominant and subordinate male mice behave differently when exposed to a female, with subordinates showing impairment of their sexual performance in the presence of the male antagonist. In the present study, we investigate whether these rank-related behavioral differences can be modified by an anxiolytic treatment. In a first experiment, diazepam (0.25 mg/kg) improves the performance of subordinate mice toward the female, as shown by the increase of proxemic behavior, anogenital sniffing, and social grooming of the female. Social grooming of the female is the only behavior modified by a higher dose of the anxiolytic drug (0.5 mg/kg). A second experiment, in which dominant and isolated mice are subjected to the same experimental procedure, demonstrates that social behavior of these two classes of males is not affected by the pharmacological treatment. The results are discussed in terms of the advantages of using subordinate males in such a sexual context as a model for the study of anxiolytic drugs.
Neuroscience, 2006
The role of voltage-gated Ca2+ (CaV) channels in pain mechanisms has been the object of intense i... more The role of voltage-gated Ca2+ (CaV) channels in pain mechanisms has been the object of intense investigation using pharmacological approaches and, more recently, using mutant mouse models lacking the CaVαl pore-forming subunit of N-, R- and T-type channels. The role of P/Q-type channels in nociception and pain transmission has been investigated by pharmacological approaches but remains to be fully elucidated.
Ethology Ecology & Evolution, 1993
Developmental Brain Research, 1999
The long-term effects of postnatal manipulation on nociception were studied in NMRI albino male m... more The long-term effects of postnatal manipulation on nociception were studied in NMRI albino male mice. During the first two weeks of life, pups were removed from their cage and deprived of maternalrnest odour for 15 minrday. To evaluate pain sensitivity, adult mice Ž. exposed to this postnatal manipulation CB group were tail flick and formalin tested for acute and tonic pain, respectively. CB mice showed a reduced pain sensitivity both in tail-flick and in formalin tests in comparison with control animals. Moreover, responsiveness to Ž. Ž. Ž. morphine MO 1.0, 2.5, and 5.0 mgrkg, i.p. in young 35 days old and adult 90 days old postnatally manipulated animals was evaluated with the tail-flick test: a decrease of the antinociceptive effects induced by morphine both in young and adult males was observed in postnatally manipulated animals. Morphine induced significant analgesic effects in control mice at doses lower than those affecting nociceptive thresholds both in young and adult CB mice. In addition, young animals showed a higher sensitivity to morphine than adults, independently of postnatal manipulation. The long-term effects of postnatal manipulation on nociception are discussed in terms of involvement of the opioid system and of the characteristics of pup manipulation.
Brain Research, 1996
The effect of the administration of the muscarinic cholinergic agonist oxotremorine on locomotor ... more The effect of the administration of the muscarinic cholinergic agonist oxotremorine on locomotor activity was investigated in DBA/2 mice subjected to chronic restraint stress of different durations (120 min daily for 10, 14 or 18 days). Oxotremorine induced a depressant effect on locomotion, which was reduced after 10 and 14 days of restraint, but not after a 18-day restraint stress. Acetylcholine (ACh) content was significantly reduced in prefrontal cortex after 10 and 14 days of stress but returned to control values after 18 days of restraint. No changes in ACh content were observed in nucleus accumbens and striatum. These results are discussed in terms of possible changes in muscarinic receptor sensitivity.
Animal Behaviour, 1991
A series of experiments was conducted to investigate whether the poorer sexual performance of sub... more A series of experiments was conducted to investigate whether the poorer sexual performance of subordinate than dominant male mice, Mus domesticus, was linked to lower sexual motivation. Ultrasonic calls uttered by a male in the presence of a female were used as an index of sexual interest. Males were housed in pairs for 5 days and dominant/subordinate roles were assigned. Subordinates, when tested in their home cage immediately after the removal of the dominant male, uttered more ultrasounds than the latter. When the dominant male was tested before the subordinate, there was no difference in the number of ultrasounds uttered and the subordinates' performance was consistently poorer. The fewer calls recorded when subordinate males were tested after the dominant partner was not associated with less defence/ escape behaviour, nor could it be explained as habituation to female odour, as a consequence of being tested after the dominant partner. Within sexually experienced pairs, the urine of dominant males interacting with a female for 3 min reduced the number ofultrasounds uttered by the subordinate in the presence of a female. It is suggested that an inhibitory factor in the dominant male's urine functions as an indirect competitive mechanism when direct competition is prevented by removing the dominant subject.
Developmental Psychobiology, 2021
Early life experiences and genetic background shape phenotypic variation. Several mouse models ba... more Early life experiences and genetic background shape phenotypic variation. Several mouse models based on early treatments have evaluated short- and long-term phenotypic alterations and explored their molecular mechanisms. The instability of maternal cues was used to model human separation anxiety in outbred mice, one of the etiopathogenetic factors that predict panic disorder (PD). Application of the repeated cross-fostering (RCF) protocol to inbred strains (C57 and DBA) allowed us to measure differential responses to the same experimental manipulation. Ultrasounds emitted during isolation indicated that after RCF, pups from both strains lose their ability to be comforted by nest cues, but the frequency modulation of separation calls increased in RCF-C57 and decreased in RCF-DBA mice. No strain-specific difference in olfactory ability explained these responses in RCF-exposed mice. Rather, disruption of the infant-mother bond may differentially affect separation calls in the two strains. Moreover, the RCF-associated increased respiratory response to hypercapnia-an endophenotype of human PD documented among mice outbred strains-was replicated in the C57 strain only. We suggest that RCF-induced instability of the early environment affects emotionality and respiratory physiology differentially, depending on pups' genetic background. These strain-specific responses provide a lead to understand differential vulnerability to emotional disorders.
Scientific reports, Feb 2, 2018
Respiratory and emotional responses to blood-acidifying inhalation of COare markers of some human... more Respiratory and emotional responses to blood-acidifying inhalation of COare markers of some human anxiety disorders, and can be enhanced by repeatedly cross-fostering (RCF) mouse pups from their biological mother to unrelated lactating females. Yet, these dynamics remain poorly understood. We show RCF-associated intergenerational transmission of COsensitivity in normally-reared mice descending from RCF-exposed females, and describe the accompanying alterations in brain DNA methylation patterns. These epigenetic signatures were compared to DNA methylation profiles of monozygotic twins discordant for emotional reactivity to a COchallenge. Altered methylation was consistently associated with repeated elements and transcriptional regulatory regions among RCF-exposed animals, their normally-reared offspring, and humans with COhypersensitivity. In both species, regions bearing differential methylation were associated with neurodevelopment, circulation, and response to pH acidification pro...
Novartis Foundation Symposia
It has been observed that &am... more It has been observed that 'No aspect of human behavioral genetics has caused more confusion and generated more obscurantism than the analysis and interpretation of various types of non-additivity and non-independence of gene and environmental action and interaction' (Eaves LJ et al 1977 Br J Math Stat Psychol 30:1-42). On the other hand, a bulk of newly published studies appear to speak in favour of common and frequent interplay--and possibly interaction--between identified genetic polymorphisms and specified environmental variables in shaping behavior and behavioral disorders. Considerable interest has arisen from the introduction of putative functional 'endophenotypes' which would represent a more proximate biological link to genes, as well as an obligatory intermediate of behavior. While explicit criteria to identify valid endophenotypes have been offered, a number of new 'alternative phenotypes' are now being proposed as…
Hippocampus, 2011
Mice born from high care-giving females show, as adults, low anxiety levels, decreased responsive... more Mice born from high care-giving females show, as adults, low anxiety levels, decreased responsiveness to stress, and substantial improvements in cognitive function and hippocampal plasticity. Given the relevance of this issue for preventing emotional and cognitive abnormalities in high-risk subjects, this study examines the possibility to further enhance the beneficial effects observed in the progeny by augmenting maternal care beyond the highest levels females can display in standard laboratory conditions. This was produced by placing a second female with the dam and its litter in the rearing cage from the partum until pups weaning. Maternal behavior of all females was scored during the first week postpartum, and behavioral indices of emotionality, prestress and poststress corticosterone levels, cognitive performance, and hippocampal morphology were assessed in the adult offspring. We found that pups reared by female dyads received more maternal care than pups reared by dams alone, but as adults, they did not exhibit alterations in emotionality or corticosterone response estimated in basal condition or following restraint stress. Conversely, they showed enhanced performance in hippocampal-dependent tasks including longterm object discrimination, reactivity to spatial change, and fear conditioning together with an increase in dendritic length and spine density in the CA1 region of the hippocampus. In general, the beneficial effects of dyadic maternal care were stronger when both the females were lactating. This study demonstrates that double-mothering exerts a longterm positive control on cognitive function and hippocampal neuronal connectivity. This experimental manipulation, especially if associated with increased feeding, might offer a concrete possibility to limit or reverse the consequences of negative predisposing conditions for normal cognitive development. V
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Papers by Francesca Damato