Biomedical subjects

G Laviola

Publications and source records attributed to G Laviola.

At least 19 recordsLinked to original sources

PubMed2006

1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence.

Administration of methylphenidate (MPH, Ritalin) to children affected by attention deficit hyperactivity disorder (ADHD) is an elective therapy, which however raises concerns for public health, due to possible persistent neuro-behavioral alterations. We investigated potential long-term consequences at adulthood of MPH exposure during adolescence, by means of behavioral and brain MRS assessment in drug-free state. Wistar adolescent rats (30- to 44-day-old) were treated with MPH (0 or 2 mg/kg once/day for 14 days) and then left undisturbed until adulthood. Levels of impulsive behavior were assessed in the intolerance-to-delay task: Food-restricted rats were tested in operant chambers with two nose-poking holes, delivering one food pellet immediately, or five pellets after a delay whose length was increased over days. MPH-exposed animals showed a less marked shifting profile from the large/late to the small/soon reward, suggesting reduced basal levels of impulsivity, compared to controls. In vivo MRI-guided 1H MRS examinations at 4.7 T in anaesthetised animals revealed long-term biochemical changes in the dorsal striatum (STR), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of MPH-exposed rats. Notably, total creatine and taurine, metabolites respectively involved in bioenergetics and synaptic efficiency, were up-regulated in the STR and conversely down-regulated in the NAcc of MPH-exposed rats. A strong correlation was evident between non-phosphorylated creatine in the STR and behavioral impulsivity. Moreover, unaltered total creatine and increased phospho-creatine/creatine ratio were detected in the PFC, suggesting improved cortical energetic performance. Because of this enduring rearrangement in the forebrain function, MPH-exposed animals may be more efficient when faced with delay of reinforcement. In summary, MPH exposure during adolescence produced enduring MRS-detectable biochemical modifications in brain reward-related circuits, which may account for increased self-control capacity of adult rats.

Animals↗

PubMed2005

Sub-neurotoxic neonatal anoxia induces subtle behavioural changes and specific abnormalities in brain group-I metabotropic glutamate receptors in rats.

Anoxia in the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. We set-up a model of subneurotoxic anoxia based on repeated exposures to 100% nitrogen during the first 7 days of post-natal life. This mild post-natal exposure to anoxia specifically modified the behaviour of the male adult rats, which showed an attention deficit and an increase in anxiety, without any impairment in spatial learning and any detectable brain damage (magnetic resonance imaging and histological analysis). Post-anoxic rats showed a reduction in the expression of group-I metabotropic glutamate receptors (i.e. mGlu1 and mGlu5 receptors) in the hippocampus and cerebral cortex, whereas expression of the mGlu 2/3 receptors, the NR1 subunit of NMDA receptors, and the GluR1 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors was unchanged. mGlu1 and mGlu5 receptor signalling was also impaired in postanoxic rats, as revealed by a reduced efficacy of the agonist (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) to stimulate polyphosphoinositide hydrolysis in hippocampal slices. We conclude that rats subjected to subneurotoxic doses of anoxia during the early post-natal life develop behavioural symptoms that are frequently encountered in the inattentive subtype of the attention deficit hyperactivity disorder, and that group-I mGlu receptors may be involved in the pathophysiology of these symptoms.

Animals↗

PubMed2004

Social withdrawal, neophobia, and stereotyped behavior in developing rats exposed to neonatal asphyxia.

Perinatal asphyxia is a concern for public health and may promote subtle neuropsychiatric disorders. Anoxic insults to neonatal rats cause long-lasting neurobehavioral deficits. In the present study, we focussed on changes in emotional behaviors as a consequence of neonatal asphyxia in Wistar rats. Newborn pups (24 h after birth) underwent a single 30-min exposure to a 100% N2 atmosphere (or air). The offspring was tested for a) locomotor and exploratory activity with or without a d-amphetamine challenge (0, 1, or 2 mg/kg) on postnatal day (pnd) 15; b) social interactions and novelty seeking during adolescence; c) levels of the brain-derived neurotrophic factor (BDNF). In the open-field test (pnd 15), N2-exposed pups injected with the high (2 mg/kg) amphetamine dose exhibited reduced levels of locomotor hyperactivity, and a more marked involvement in stereotyped behaviors. Individual differences emerged in the locomotor response to the novelty-seeking test: two subgroups of rats (separated on the basis of the median value) showed either arousal/attraction or avoidance/inhibition in response to free-choice novelty. The N2-exposed group showed a more marked novelty-induced avoidance and inhibition. Time devoted to allogrooming and play-soliciting behaviors was reduced, whereas object exploration was increased. Levels of BDNF were reduced in the striatum of N2-exposed rats, suggesting poorer synaptic performance of dopamine pathways. In conclusion, these findings suggest an increased risk of developing social withdrawal, neophobia and behavioral stereotypies (common symptoms found in schizophrenia and autism) as a consequence of neonatal asphyxia in preterm humans.

Analysis of Variance↗

PubMed2004

Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats.

Prenatal stress in the rat induces enhanced reactivity of the hypothalamus-pituitary-adrenal (HPA) axis, disturbances in a variety of circadian rhythms and increased anxiety-like behaviour. Such abnormalities parallel those found in human depressed patients. Prenatally stressed (PS) rats could represent, therefore, an interesting animal model for the evaluation of the efficacy of pharmacotherapeutic intervention in psychiatric disorders that has often been addressed using control animals. In the present study, PS and non-stressed rats were chronically treated with the tricyclic antidepressant imipramine (10 mg/kg i.p. for 21 days) and assessed in the forced swim test. Glucocorticoid receptor binding sites in the hippocampus were measured and 5-HT(1A) receptor mRNA levels in the frontal cortex were also assessed. PS rats were characterised by increased immobility in the forced swim test, reduced hippocampal corticosteroid receptor binding and increased levels of cortical 5-HT(1A) mRNA. All these parameters were significantly reversed by chronic imipramine treatment. Conversely, no significant effects were observed for non-stressed rats. All these effects are consistent with the expected pharmacotherapy of depression-like abnormalities in PS rats. These results further indicate that PS rats are a relevant animal model of depression.

Animals↗

PubMed2004

Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model.

Adolescence comes in association with puberty, when maturation and rearrangement of major neurotransmitter pathways and functions are still taking place. The neurobiological processes occurring in the brain during this developmental period have been so far poorly investigated. Yet, it is during adolescence that some major neuropsychiatric disorders may become evident, including ADHD, schizophrenia, and drug abuse. Moreover, the age-related neurobehavioural plasticity renders adolescents particularly vulnerable to the consequences of psychoactive drug exposure. In this view, there is an increased likelihood that addiction will develop when psychoactive drug use starts early during adolescence. From all these observations adolescence emerges as a critical phase in development. In the present review, we focus on recent neurobiological characterization of adolescent rats and mice. As for vulnerability to addictive behaviour, nicotine exposure during adolescence dose-dependently down-regulated levels of AMPA GluR2/3 subunits in the striatum, suggesting a reduced neurobehavioural plasticity in adult subjects. Comparable exposure during adulthood had opposite effects. It was found consistently that exposure to nicotine during adolescence, but not similar exposure in the post-adolescent period, increased the expression of specific subunits of the acetylcholine receptor in adult rats, thus enhancing the reinforcing efficacy of nicotine in a self-administration paradigm. The present data identified a specific age-window, characterized by long-term effects on behavioural and neurochemical indexes, of vulnerability. With respect to potential therapeutic approaches in ADHD, we studied the adolescent spontaneously-hypertensive-rat (SHR) in an intolerance-to-delay operant-behaviour paradigm. The model was further validated by the finding that impulsivity was reduced by chronic methylphenidate administration. Impulsive SHR animals were characterized by reduced cannabinoid CB1 receptor density in the prefrontal cortex. Interestingly, an acute cannabinoid agonist increased levels of self-control behaviour in these animals. The present data suggest that pharmacological modulation of the cannabinoid system might improve some behavioural anomalies seen in ADHD. In conclusion, modelling the adolescent phase in rats and mice appears to be useful for the investigation of determinants of vulnerability to addiction and to other early-onset neuropsychiatric disorders.

Adolescent↗

PubMed2001

Novelty seeking in periadolescent mice: sex differences and influence of intrauterine position.

In rodents, beside basic sex differences, a certain degree of within-gender phenotypic variation can also be provided in utero by hormones from adjacent fetuses. We investigated novelty-seeking behavior in two groups of male and female mice from know intrauterine position: 2M (between males) and 0M (between females). Subjects were assessed during periadolescence (postnatal days 33--43), an ontogenetic phase, which is characterized by an elevated expression of this novelty-seeking behavior. Periadolescent mice underwent a familiarization session for 3 consecutive training days with one side of a two-chamber apparatus. On testing day 4, the opening of a partition, which allowed mice to freely move from the familiar compartment to a novel one, produced an increased behavioral arousal in all animals. Marked sex differences were found, with females being in general more active than males, whereas the latter showed significantly higher levels of novelty seeking than females. Uterine position failed to affect the profile of novelty preference in females, whereas within the male group 2M subjects expressed a marked profile of novelty seeking. The differential titers of sex hormones reported to characterize the 0M and 2M condition early in fetal development are suggested to account for the individual variability in the seeking for novelty within the male group during puberty.

Adaptation, Psychological↗

PubMed2001

delta-Opioid modulation of social interactions in juvenile mice weaned at different ages.

The environmental stimulus of weaning has been shown to affect both the developmental expression of social behavior and the maturation of the opioid delta-receptors' subpopulation in altricial rodents. The aim of this study was to address both these issues by using the social interaction paradigm. Separate groups of male and female mice were randomly assigned to three different weaning ages -- early (Wean-15), regular (Wean-20), and delayed (Wean-25) -- and assessed when 30 days old under intraperitoneal administration of the selective delta-opioid agonist SNC80 (0, 0.1, or 0.3 mg/kg). Wean-15 male and female subjects were much more involved in investigating the partner as well as the cage environment compared to the regular Wean-20 group. An increased social investigation was also found as a consequence of delayed weaning in the female group. The neurobehavioral changes induced by the manipulation of weaning age were also reflected in an altered responsivity to the effects of SNC80 administration. The drug-induced increase in the expression of investigative and affiliative social interactions was further magnified by early weaning. A delayed weaning time was instead associated with reduced sensitivity to the drug, which suggests a delayed maturation of the system. As a whole, the present results indicate that the time of weaning is able to markedly affect the expression of social interactions of adolescent mice by possibly exerting a direct modulatory role on the development of the still plastic delta-opioid system.

Aging↗

PubMed2001

Striatal dopamine sensitization to D-amphetamine in periadolescent but not in adult rats.

The neurobiological and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants. Periadolescent (33-43 days) and adult (>70 days) Sprague-Dawley rats underwent a 3-day treatment history with D-amphetamine (AMPH) at 0, 2, or 10 mg/kg (once a day). After a short 5-day-long withdrawal interval, freely moving animals were challenged with a 2-mg/kg AMPH dose and their behavior as well as in vivo intrastriatum dopamine (DA) release in the CNS were assessed. Microdialysis data indicated that AMPH-history periadolescent rats showed a prominent sensitization of AMPH-stimulated DA release, whereas no such change was found in adult subjects. As expected, acute AMPH administration strongly reduced time spent lying still and increased levels of cage exploration in animals of both ages. A treatment history of high AMPH dosage was associated with a marked sensitization of the exploratory behavior in adults, whereas it induced a quite opposite profile in periadolescents. The latter group only was also characterized by a compulsive involvement in the stereotyped head-bobbing response. These results indicate that differently from adults, marked alterations in neurobiological target mechanisms are observed in rats around periadolescence as a consequence of a quite mild regimen of intermittent AMPH exposure. Thus, a neurobiological substrate for an age-related increased vulnerability towards the addictive risks of these drugs is suggested.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Experimentally induced aggressive behavior in subjects with 3,4-methylenedioxy-methamphetamine ("Ecstasy") use history: psychobiological correlates.

PURPOSE: Objective measures of experimentally induced aggressiveness were evaluated in 12 male 3,4-methylenedioxy-methamphetamine (MDMA, "Ecstasy") users, in comparison with 20 healthy male subjects. METHODS: All the subjects were preliminarily submitted to DSM-IV interviews and Buss-Durkee Hostility Inventory (BDHI). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money that was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Escape responses were also possible protecting the counter from monetary subtractions. RESULTS: Money-earning responses were not different in Ecstasy users and controls; aggressive responses were significantly higher in Ecstasy users in comparison with control subjects (F=20.74, P<.001). Baseline adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were higher in Ecstasy users than in controls. No difference was found in norepinephrine (NE) and epinephrine (EPI) basal levels of the two groups. During the experimentally induced aggressiveness, plasma ACTH concentrations increased significantly less and NE and EPI levels, together with heart rate (HR), increased significantly more in Ecstasy users than in healthy subjects. Despite ACTH-blunted responses, CORT did not increase differently from controls in Ecstasy users. PSAP aggressive responses positively correlated with catecholamines and CORT changes, BDHI Direct Aggression and Irritability scores, both in Ecstasy users and controls. A significant correlation was found between Ecstasy exposure extent and aggressive responses (r=.78, P<.001). IMPLICATIONS: Our findings suggest that Ecstasy users have higher outward-directed aggressiveness than healthy subjects. Aggressiveness in MDMA subjects seems to be associated more with MDMA pharmacological effects than with personality traits: Nevertheless, a premorbid psychobiological proneness to aggressive behavior cannot be excluded. Increased catecholamines reactivity, basal hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, and blunted ACTH responses could be due to MDMA action on monoaminergic pathways and adrenal function.

Adolescent↗

PubMed2001

[Impact of socio-environmental factors on physiological processes of brain damage recovery: contribution of animal models].

This review presents the experimental approaches more widely used in animal models to investigate possible strategies aimed to stimulate plasticity in the nervous system and possibly to increase spontaneous recovery from functional/neurological diseases such as neonatal anoxia. Methods used in laboratory rodents are briefly described. Attention is focused on possible enrichments of the social and physical environment during the development.

Animals↗

PubMed2000

Neuroendocrine correlates of depression in abstinent heroin-dependent subjects.

The functions of the central alpha-adrenergic, serotoninergic and dopaminergic systems were investigated in 28 heroin-dependent subjects 6-8 weeks after detoxification, and in 22 healthy control subjects (group C). Fourteen heroin-dependent subjects with depressive comorbidity (group A), and 14 heroin-dependent subjects without other Axis I and II pathologies (group B) were included among abstinent substance abusers. Norepinephrine (NE) function was evaluated by growth hormone (GH) responses to acute stimulation with clonidine (clon); serotonin (5-HT) function by prolactin (PRL) and cortisol (CORT) responses to acute stimulation with D-fenfluramine (D-fen) and dopamine (DA) function by GH and PRL responses to acute administration of bromocriptine (brom). Central NE activity, as measured by the GH-clon test, seems to be well preserved both in A and B subjects. PRL and CORT responses to D-fen were significantly blunted both in A subjects and in B subjects, in comparison with control subjects (C); the PRL response in A subjects was significantly lower than in B subjects. The DA system of B subjects was found unimpaired; in contrast, a significantly higher GH response to brom in A subjects (depressed) could express D2 post-synaptic receptor hypersensitivity and, therefore, decreased pre-synaptic DA release. In sum, the study of central monoamine function revealed an alteration only of the 5-HT system in detoxified heroin-dependent subjects without psychiatric comorbidity, which might be a trait character of these subjects, possibly involved in the pathogenesis of the disorder. A more significant impairment of 5-HT function and the hypersensitivity of post-synaptic DA receptors in A subjects suggests that specific biological correlates of psychiatric comorbidity may characterize substance abuser subtypes.

Adrenergic alpha-Agonists↗

PubMed2000

A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice.

The identification of critical ontogenetic periods of increased vulnerability to the effects of drugs of abuse could have a great psychobiological and clinical-therapeutical importance. Potential age-related differences in the response of the hypothalamic-pituitary-adrenal (HPA) axis to both stress and psychostimulants has been tested here in an animal model of adolescence. Periadolescent (PND 33-43) and Adult (PND>60) mice of both sexes were injected with d-amphetamine (AMPH, 0, 2, or 10 mg/kg i.p.) and immediately faced with a mild psychological stress experience, i.e. placement in a novel environment. A detailed time-course analysis of both hormonal and behavioral profiles was performed, with animals being sacrificed for trunk-blood collection at different time-points during the test (before the injection, NT group; 15, 30, or 120 min after the injection). Basal corticosterone (CORT) levels (NT group) were consistently higher in periadolescents than in adults. As a whole, a marked increment of blood CORT levels was found in mice of both ages exposed to forced novelty. However, important age-related differences were also observed, with Saline-injected periadolescents still exhibiting elevated levels of locomotion at the end of the 120-min test session and failing to show the increasing profile of CORT release over the baseline that was typical of adults. Upon an AMPH 2 administration, periadolescents exhibited a much lower profile of locomotor hyperactivity than adults, and also failed to show an increase across the course of the session in CORT release, that was observed in adults. When treated with the high AMPH 10 dose, a marked locomotor hyperactivity was found in periadolescents, which however showed much lower levels of the stereotyped licking and gnawing behavior, that was typical of adults. The present results suggest a unique profile of integrated behavioral and physiological hyporesponsivity in mice during periadolescence. The latter also represents a very useful model for the study of the issue of psychobiological risk factors involved in vulnerability to drugs of abuse in human adolescents.

Analysis of Variance↗

PubMed2000

Paradoxical effects of D-amphetamine in infant and adolescent mice: role of gender and environmental risk factors.

The psychostimulant D-amphetamine (AMPH) increases generalised activity in adult subjects, while exerting a paradoxical "calming effect" in children with Attention-deficit Hyperactivity Disorder (AD/HD). A number of animal models have been developed to characterise the neurobiological basis of this AMPH action. In this line, the present review summarises recent work on the effects of AMPH on behavioural and physiological parameters in developing mice with a special emphasis on the role of gender and environmental risk factors. Behavioural and neuroendocrine responses to AMPH administration (0, 1, or 3 mg/kg, IP) and their relation to changes in the environment, represented by social stimuli, were studied in infant CD-1 mouse pups of both sexes at three different developmental ages (3, 8, or 18 postnatal (pnd) days). Mouse pups were assessed either in baseline condition or following 24 h maternal deprivation. AMPH exerted a paradoxical effect on CORT secretion only in maternally deprived subjects while affecting behaviour mainly in deprived female subjects, which showed a generalised shift to the left in the dose-response curve to this drug. Unwanted perseverative motor effects and possible dependence states represent side effects of AMPH administration. Further knowledge on these aspects comes from another set of studies where a shortened conditioned place preference (CPP) paradigm was employed to assess the reinforcing properties of AMPH (0, 1, 3.3, or 10 mg/kg) in developing mice on 14-17, 21-24, and 28-31 pnd. Data indicate that AMPH-CPP develops early, mice being able, already at two weeks of age, to acquire a place preference that relies on adult-like sensory, motor, and associative capacities. AMPH-CPP appears earlier in females, compared to males. A detailed analysis of acute D-amphetamine effects evidenced that the drug produces a dose-dependent increase in locomotor activity and in several responses (including stereotypes). These effects appear much larger at both post weaning stages than in preweanlings and are significantly more pronounced in females than in males. Overall these data suggest that AMPH action is dependent on the baseline level of activity and indicate a strong role of gender in the effects of this drug measured early on during development, with females showing greater sensitivity to this drug. A better understanding of AMPH action during the early ontogenetic phases, particularly its interaction with environmental factors, might extend our knowledge on the neurobiological basis of AD/HD, possibly improving the clinical efficacy of psychostimulant drugs.

Aging↗

PubMed2000

Attractivity and social preferences in mice (Mus musculus domesticus): the role of prepubertal sexual segregation and of precocious weaning.

Mice (Mus musculus domesticus) were raised (Postnatal Day 15 to 25) in single- or mixed-sex litters and precociously (Day 15) or regularly (Day 25) weaned. When they were faced as adults with a basic social choice--between two stimulus mice raised in litters of different sex composition but both of the same sex as the chooser--mice raised in mixed-sex litters were preferred. In the sociosexual choice-between a male and a female, both from the single- or the mixed-sex group--the opposite-sex preference was expressed. Both these preferences were abolished by the sexual segregation of the choosers. This variable hardly affected potential mate choice--between two stimulus mice both of the opposite sex of the chooser but raised in litters of different sex composition. Data indicate that socially mediated behavioral plasticity has a major role in the early shaping of adult individual differences both in attractive stimulus properties and in sociosexual preferences.

Animals↗

PubMed2000

[Psychobiologic risk factors and vulnerability to psychostimulants in adolescents and animal models].

Adolescent↗

PubMed1999

Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models.

Adolescence is associated with an increased risk of developing drug abuse/dependence. During this ontogenetic phase, brain and hormonal systems are still undergoing crucial maturational rearrangements, which take place together with significant modifications in psychosocial development. However, the neurohormonal and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants such as MDMA ("Ecstasy") and amphetamine (AMPH). Novelty-seeking, a temperamental/behavioral trait that is typical of this age period, might substantially contribute to both psychological and psychobiological vulnerability. In humans, an elevated score of novelty-sensation seeking and a derangement of monoaminergic function were both associated with late adolescence MDMA users compared to controls. In animal models of periadolescence, the search for novel stimuli and sensations actually shares a common neurobiological substrate (the reward-related brain mesolimbic pathways) with psychostimulants. The present review summarises recent work in mice, which indicates that periadolescent subjects are characterized by an unbalanced and "extremes-oriented" behavior and by elevated novelty-seeking compared to adults. Repeated and intermittent administration of cocaine or AMPH was associated with the development of a prominent locomotor sensitization in periadolescents, which failed to exhibit the marked sensitization of the stereotyped behavioral syndrome--possibly associated with poor welfare--that was typical of adults. A unique profile of integrated behavioral and physiological hyporesponsivity to both forced novelty and acute AMPH administration during periadolescence was also found. As a whole, these results, together with previous work on this topic, suggest that periadolescents may be more "protected" from AMPH-related aversive properties, and perhaps more vulnerable to the experience of internal states of reward, than older animals. Thus, the present animal model of adolescence seems to represent a reliable and useful method for the investigation of vulnerability to a variety of habit-forming agents or emotional experiences whose positive reinforcing properties may rely on common neurobiological substrates. A deeper understanding of psychostimulant effects during adolescence on the complex interaction between genetic, neurobiologic, psychosocial, and environmental factors will lead to earlier and more effective prevention and treatment.

Adolescent↗

PubMed1999

Behavioral and hormonal effects of partner familiarity in periadolescent rat pairs upon novelty exposure.

In periadolescent rats, social interactions are typically characterized by elevated levels of playful and affiliative behavior. Aim of the present study was to assess the behavioral and hormonal effects of partner familiarity upon the separation and reunion in a novel environment of established pairs of periadolescent subjects. At weaning (post-natal day, PND 21), Sprague-Dawley rats were pair housed with a non-sibling subject of the same age and sex. On PND 35, the members of each pair were separated for a 24-h period, and randomly assigned to different experimental groups: (1) sacrificed before separation; (2) sacrificed immediately after the isolation period; (3-4) placed individually in a novel cage for 30 min either in low-light or in high-light conditions; (5-6) reunited for 30 min in a novel cage either with their previous cagemate (familiar, FAM); or (7-8) with an unfamiliar rat (UNF) of the same age and sex, in either light conditions. During reunion, the occurrence of social and non-social behaviors was scored. Blood samples were collected at the end of the session from all groups and assayed for corticosterone (CORT). The separation of the two members of an established pair did not affect baseline CORT levels. Upon reunion, the presence of a conspecific exerted a significant buffering effect on the novelty-induced increase in CORT levels. Such an effect of the social companion appeared more marked in males than in females, and in FAM compared to UNF pairs. Interestingly, FAM rats also expressed a significantly higher amount of social investigation and play-soliciting behavior compared to UNF animals. Behavioral results, together with previous data, suggest that periadolescent rats housed in established pairs develop a sort of amicable relationship. The overall CORT output measured at the end of the session is also in line with this interpretation. As a whole, these findings indicate that periadolescence is a time period during rat development, during which social variables play a very important role in modulating both behavioral and physiological responses to novelty in a fashion that does not completely overlap with data on adult subjects.

Animals↗

PubMed1998

Evaluation of unconditioned novelty-seeking and d-amphetamine-conditioned motivation in mice.

Following repeated association between psychostimulant drugs and a distinct environment, contextual cues acquire the ability to elicit a conditioned approach response. Further, both rats and mice have a natural drive to seek for the experience of novelty, and a previously unknown environment is able to elicit an unconditioned approach response. Both the experience of novelty and amphetamine (AMPH)-conditioned effects have been associated in rodents with the activation of brain meso-limbic dopaminergic pathways. This study assessed the relative strength of AMPH-conditioned and novelty-induced unconditioned motivations in mice. During the pretreatment period, mice were randomly assigned to three different treatment history groups, and received d-AMPH (0, 2, or 10 mg/kg i.p. once/day) injections for 3 days in the presence of a familiar environment. Following a 48-h washout from the last drug injection, animals were placed in the familiar and pretreatment-paired environment and challenged with either SAL (to evaluate conditioning) or a standard AMPH dose (2 mg/kg, to assess either acute drug effects or carryover influences of each animal's treatment history with the same drug). Following the opening of a partition, animals showed both a clear-cut preference for a novel environment as well as a marked novelty-induced hyperactivity. Interestingly, when mice were tested in a drug-free state in this free-choice paradigm, they expressed neither conditioning to the drug-associated environment nor carry-over effects on the novelty-induced hyperactivity profile. On the other hand, mice injected with AMPH showed a mixed profile, with AMPH 2 treatment history mice showing a conditioned preference for the familiar and drug-paired environment, whereas AMPH 10 animals preferred to spend more time in the novel compartment. Both AMPH doses were associated with an increased locomotion, whereas only the AMPH 10 dose resulted in a stereotyped behavioral syndrome, possibly reminiscent of an aversive "poor welfare" condition. Thus, as a function of the drug dosage, differential positive or negative incentive properties are suggested to be evoked by the AMPH-conditioned environment. In conclusion, a reliable and useful experimental paradigm has been developed to investigate the issue of vulnerability to a variety of habit-forming agents or emotional experiences whose positive reinforcing properties may rely on a common neurobiological mechanism.

Animals↗