Biomedical subjects

Giovanni Laviola

Publications and source records attributed to Giovanni Laviola.

43 records · Page 3Linked to original sources

PubMed2002

Peculiar response of adolescent mice to acute and chronic stress and to amphetamine: evidence of sex differences.

Although final brain size and the number of available neurons and axons appear to be established early in infancy, plasticity of the brain continues during adolescence through an integrated process of overproduction and elimination of synapses and receptors. In addition, hormonal levels change dramatically during this period, as a result of the onset of puberty. This age-specific condition has been suggested to serve as a permissive factor for the emergence of a number of early-onset neuropsychiatric disorders, including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and perhaps substance abuse. However, relatively few investigations have focused on animal models of this developmental phase. The periadolescent rodent (similar30-45-day-old), has been proposed as a useful model. Periadolescent rats and mice are generally associated with a peculiar behavioral profile, consisting of basal hyperactivity, high attraction towards novel stimuli and a marked involvement in affiliative and playful behaviors. Moreover, a unique profile of psychopharmacological responsivity characterizes rodents around this age. Recent experiments by our group investigated age-related discontinuities in the response of the hypothalamic-pituitary-adrenal axis (HPA) to both stress and psychostimulants. The latter are often administered as therapeutic drugs to children with ADHD, which have been also associated with an impaired response to stress and abnormalities in HPA axis function. Indeed, an altered functioning of the HPA axis has been proposed as a possible risk factor and a potential marker for such a behavioral vulnerability. Animals were studied at adulthood (> pnd 70) or during periadolescence. Experiment I characterized basal corticosterone (CORT) levels in naive mice kept undisturbed in standard social conditions from weaning to sacrifice. Periadolescent male mice showed higher basal CORT levels than adult subjects, suggesting that the set up of the HPA axis is physiologically elevated during adolescence. In experiment II, we investigated age-related differences in the response to both acute and chronic stress conditions. Periadolescent and adult mice were housed either in a standard (three animals per cage) or in a crowding condition (nine animals per cage). The latter has been indeed reported to potentiate the subsequent reaction to acute stress in adult rodents. At the end of this period and following 24 h individual housing, mice were injected with either saline (SAL) or a standard amphetamine (AMPH) dose (2 mg/kg), and faced with a mild acute psychological stress, namely removal of sawdust from the home cage. Important sex differences emerged in animals of the two ages. Periadolescent females showed a reduced CORT response to acute stress. Within the adult male group, the chronic crowding condition produced a prominent potentiation of CORT response to the acute stress challenge. Conversely, this profile was not evidenced in periadolescents. These results indicate a strong role for gender and social variables in the response of periadolescent subjects to the various aspects of stress. As for AMPH effects, in the absence of significant changes in adult subjects, the drug produced a marked CORT release in periadolescent mice. A better understanding of neuroendocrine-related AMPH effects as a function of social and environmental risk factors during adolescence, might deepen our knowledge on the neurobiological bases of genetically determined neuropsichiatric disorders and possibly improve the therapeutical efficacy of psychostimulant drugs.

Acute Disease↗

PubMed2002

Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence.

A "gateway" function toward substance abuse has been suggested for early tobacco smoking. Nicotine actually represents an easily available drug for human adolescents, who are very likely to use a number of different psychoactive agents. Surprisingly, the psychobiological factors involved in this age-related willingness have been poorly investigated. In Experiment 1, nicotine consumption was studied in outbred CD-1 mice during Early (postnatal day (pnd) 24 to 35), Middle (pnd 37 to 48) or Late (pnd 50 to 61) adolescence, in an oral self-administration paradigm. During the drinking session (2 h/day), animals had free choice between either tap water or a nicotine solution (10 mg/l). After a 6-day period, a fading study was carried out, in which nicotine concentration was reduced to 7 mg/l (days 7-9) and 5 mg/l (days 10-12), to assess whether animals would compensate by increasing their intake from the nicotine solution. In Experiment 2, psychopharmacological effects on locomotion induced by the nicotine solution (0, 10, 30 mg/l) during the 1-h drinking session were assessed in Early and Late adolescent mice. In Experiment 1, Early adolescents expressed a marked and stable preference for the nicotine solution, showing a daily nicotine intake of 1.15 +/- 0.04 mg/kg. Middle adolescents did not show any preference for either bottle, whereas a tendency toward avoidance for the nicotine solution was found for Late adolescents. In the fading study, Early adolescents were the only group to show increased consumption from the nicotine bottle as far as nicotine concentration was reduced. A time-course analysis of plasma levels of cotinine (the principal biomarker of nicotine consumption) revealed some pharmacokinetic differences between the three age-groups. In Experiment 2, drinking from a nicotine solution produced a prominent hyperactivity in Early adolescents, whereas a quite opposite profile was associated with older subjects. In summary, even if a role for taste factors cannot be completely ruled out, a peculiar spontaneous drive toward oral nicotine consumption, as well as a nicotine-induced arousal, is specific to Early adolescence in mice. The present animal model might be useful to investigate psychobiological determinants involved in early tobacco smoking in human adolescents

Adolescent↗

PubMed2002

Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning.

Individual differences in coping with novelty and in the response to psychoactive drugs have been related to early life events, such as the age of weaning. Outbred CD-1 mice underwent a precocious (postnatal day (pnd) 15, Wean-15 group), regular (pnd 21, Wean-21 group), or delayed (pnd 27, Wean-27 group) weaning, and were tested as adults (pnd > 60). In Experiment 1, animals underwent a treatment history with d-amphetamine (AMPH 0, 1, or 5 mg/kg once/day for three days) in a familiar environment. On testing day, mice were challenged with SAL or a standard 1 mg/kg AMPH dose (to evaluate acute drug effects and sensitization), and placed in the familiar environment. As expected, regular Wean-21 animals showed an AMPH-induced hyperactivity and a profile of conditioned locomotion, whereas the same dosage failed to induce any change in Wean-15 and Wean-27 groups. Levels of spontaneous novelty seeking were particularly elevated for Wean-27 mice, when compared with the other weaning groups. In Experiment 2, pairing of AMPH administration (0, 1, 2, 3.3, or 5 mg/kg once/day for three days) with a distinct environment produced a classical conditioned place preference. The magnitude of the preference profile was significantly more marked for Wean-15 mice, when compared with the other two weaning groups. Both experiments also provided evidence that the development of sensitization was particularly evident in Wean-27 mice. In summary, delayed weaning was associated in adult mice with both elevated levels of novelty seeking and increased sensitization to drug effects. Conversely, animals weaned precociously were much more responsive to AMPH-induced incentive conditioning. These results appear relevant to the issue of early experiences as possible risk factors for a number of psychiatric disorders in humans, including the abuse of drugs.

Aging↗

PubMed2002

[MDMA (ecstasy): neuroendocrine and behavioral features].

Long lasting 5HT system impairment has been demonstrated in experimental animals exposed to ecstasy use; MDMA seems to be able to induce behavioral conditioning and reiterated use because of its dopaminergic action. Among behavioral aspects of ecstasy users mood disorders, irritability and difficult in relationships, interpersonal difficulties, high levels of impulsiveness and hostility, high sensation seeking, cognitive and attentive deficit have been reported. A derangement of serotonin system function was reported also in humans exposed to ecstasy, as confirmed by neuroendocrine challenges and brain imaging techniques. Recent researches suggest functional changes in dopaminergic system too. The persistence of behavioral and neuroendocrine changes many months after MDMA's discontinuation, indicate a lack of reversibility in the dysfunction induced by ecstasy, or the persistence of psychobiological traits that could preexist to MDMA exposure, possibly involved in substance abuse vulnerability.

Behavior↗

PubMed2002

[Psychobiological determinants of risk behavior in adolescence].

Human adolescence is mainly characterised by an elevated number of psychological, biological and behavioural changes. This rapid as well as challenging change in the "inner state" during adolescence in humans seems to share a number of similarities with the age-dependent alteration of the normal and "linear" development in other mammalian species. Hence, in order to further investigate the biological bases of these idiosyncratic age-related responses, it seems worth to develop and to study suitable animal models for this developmental phase. Aim of the present review is to show experimental results indicating an elevated similarity between humans and rodents (mice and rats) in a number of psychological (elevated levels of novelty seeking as well as of harmavoidance due to a reduced anxiety) behavioural (elevated exploration of novel as well as potentially dangerous environments and peculiar vulnerability to incentive properties of drugs of abuse) and neurobiological (developing state of the underlying cortical pathways implicated in the above mentioned responses) processes. These findings could prove really useful in view of a general deeper comprehension of this age period and helpful in developing earlier and more effective prevention strategies aimed at reducing the social impact of dangerous and reckless behaviours frequently shown by human adolescents (drug addiction, undesired pregnancy. AIDS and car accident).

Adolescent↗

PubMedDate not supplied

Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence.

Epidemiological research has emphasized that adolescence is associated with some temperamental and behavioral traits that are typical of this age and that might substantially contribute to both psychological and psychobiological vulnerability. The contribution of the important developmental rearrangements in neurobiological and neuroendocrinological processes has received surprisingly little investigation. The present review summarizes recent work in animal models, indicating that adolescent rodents exhibit marked peculiarities in their spontaneous behavioral repertoire. When compared to adults, adolescents show an unbalanced and 'extremes-oriented' behavior, consisting of an increased novelty seeking, together with decreased novelty-induced stress and anxiety, an increased risk-taking behavior in the plus-maze, as well as elevated levels of impulsivity and restlessness. Age-related discontinuities in the function of monoaminergic systems, which are a main target of abused drugs, can perhaps account for such a profile. In particular, a peculiar function within reward-related dopaminergic brain pathways actually seems to underlie the search for novel and rewarding sensations, as well as changes in the magnitude of psychostimulant effects. The role played by early epigenetic factors in the shaping of novelty-seeking behavior of adolescent and adult rodents are also reviewed. Two examples are considered, namely, subtle variations in the hormonal milieu as a function of intrauterine position and precocious or delayed maturation of nutritional independence as a function of changes in time of weaning. As for spontaneous drug consumption, a prominent vulnerability to the oral intake of nicotine during early adolescence is reported. In conclusion, adolescence in rodents may represent a suitable animal model with enough face- and construct-validity. Actually, this model is able to show behavioral features that resemble those found in human adolescents, including vulnerability to the consumption of psychoactive drugs.

Adolescent↗

PubMedDate not supplied

Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents.

The present review deals mainly with the ontogenesis of two important phenomena involved in vulnerability to several neuropsychiatric disorders, namely with drug-induced sensitization (both contextual and non-contextual) and with conditioned place preference. The term 'infancy' covers the first three postnatal weeks during development in rats and mice. Conversely, the term 'adolescence' may cover the whole postnatal period ranging from weaning (PND 21) to adulthood (at least PND 60) or specifically the period around the onset of puberty (animals aged 33-44 days). Recent studies in rats demonstrated that the establishment of a context-dependent sensitization appears during the first (for repeated drug administration) or during the second (for a single drug administration) postnatal week. However, the memory of drug-context association is transient in developing pups (lasting one or two days following the drug pretreatment). The long-term retention of drug-context associations matures progressively, and is complete by the third week of postnatal life. Finally, those mechanisms responsible for an adult-like profile of context-independent pharmacological sensitization appear later during ontogenesis, being mature by the fourth week of postnatal life. Another set of experiments extended this ontogenetic characterization by comparing adolescent and adult mice. When compared to the latter, the former subjects exhibit a greater amphetamine-induced locomotor sensitization, almost no sensitization of aversive stereotyped behaviors, and a less marked place conditioning. The strength of the drug-induced place conditioning was also directly compared with the unconditioned novelty-seeking drive. In conclusion, neonatal rats are able to show a relatively short-lasting retention of sensitized drug effects (short-term sensitization), whereas the ability to exhibit relatively long-lasting sensitized effects matures progressively during infancy (long-term sensitization). On the other hand, adolescent mice show a reduced sensitization of drug-induced psychotic symptoms, together with a more marked sensitization of arousing and euphorigenic properties of the drug and a reduced incentive memory of its hedonic effects. These age-related changes do imply very different degrees of vulnerability to drug addiction and several other neuropsychiatric disorders.

Age Factors↗