Biomedical subjects

M Ammassari-Teule

Publications and source records attributed to M Ammassari-Teule.

At least 37 records · Page 2Linked to original sources

PubMed1994

Radial maze performance and open-field behaviours in aged C57BL/6 mice: further evidence for preserved cognitive abilities during senescence.

C57BL/6 mice, aged 2 or 24 months, were tested in a radial maze and observed for an 8-min period, repeated on 3 consecutive days, in an open-field situation with a novel object. In the eight-arm maze, the number of unrepeated path choices made by old mice does not significantly increase with training, whereas it does in young mice. Older animals also take significantly longer to solve the task but the two age groups do not differ with respect to how many paths they run before making the first error or in the strategies used to solve the task. In the open-field situation, the two age groups differ with regard to grooming and rearing behaviour, while in the novelty situation, older animal show a higher level of locomotor activity, perform less freezing, and interact more with the novel object. Habituation curves for all parameters, except grooming in the open field, do not differ between the two groups, thus indicating that this form of nonassociative learning does not vary substantially with increasing age. Results are discussed in terms of preserved cognitive abilities during senescence in that strain.

Aging↗

PubMed1993

Mechanical deafferentation of basal forebrain-cortical pathways and neurotoxic lesions of the nucleus basalis magnocellularis: comparative effect on spatial learning and cortical acetylcholine release in vivo.

Rats were assigned to one of the following treatments: bilateral cut of basal forebrain-cortical fibers (DEAFF), ibotenic (IBO) or quisqualic (QUIS) acid lesions of the NBM and sham operations (SHAM). They were trained to perform a radial eight-arm maze task with all the paths or only four paths baited. Cortical cholinergic release measured by microdialysis in vivo and choline acetyltransferase activity were also assessed in the four lesion conditions. The results show that, in the full baited maze task, only the DEAFF group showed a severe spatial learning impairment. In the four-baited path task, the DEAFF group was still more impaired than the other groups but a performance deficit also emerged in rats with IBO lesions. Neurochemical data indicated that cortical choline acetyltransferase activity was reduced by 25% after IBO lesions, by 52% after DEAFF and by 46% after Quis lesions. However, cortical cholinergic release, which dropped in the same fashion after DEAFF or QUIS lesions, was unaffected by IBO lesions. Thus, in spite of the distinctive patterns of behaviour exhibited by the three lesioned groups, no correlation between cortical cholinergic deficiencies and spatial learning impairment was found. The similar behavioural effects produced by DEAFF and fornix sections suggests that, among the basal forebrain-cortical pathways, descending fibers projecting onto the septo-hippocampal system could exert a strong control on spatial learning performance.

Acetylcholine↗

PubMed1993

Learning in inbred mice: strain-specific abilities across three radial maze problems.

Mice belonging to the C57BL/6, DBA/2 (DBA), and C3H/He (C3H) strains were compared in three different eight-arm radial maze tasks requiring various degrees of spatial and nonspatial information processing. The results show that, on the standard radial maze task, C57 performed better than DBA, which, in turn, performed better than C3H. Fewer differences in the four-baited arm task and no difference in the cued version task were found between C57 and DBA, while C3H still performed more poorly. The high performance shown by C57 mice in all problems seems to be related to their ability to build up maze-running patterns based upon an optimal proportion of 45 degrees angle turns, according to the demand of the situation. The cognitive and discriminative mechanisms involved in the solving of each task, the sensorial characteristics of the three strains, and the limits of an approach based upon neuroanatomical-behavioral correlations are discussed.

Animals↗

PubMed1993

Effects of oxiracetam, physostigmine, and their combination on active and passive avoidance learning in mice.

The nootropic drug oxiracetam (50 and 100 mg/kg) had no effect on one-trial passive avoidance acquisition in CD-1 mice, while the acetylcholinesterase inhibitor physostigmine improved passive avoidance performance at doses of 0.025 and 0.05 mg/kg given either pre- or posttraining. In a multitrial avoidance task (shuttle-box), a consistent tendency to better performance was displayed by mice receiving oxiracetam (50 and 100 mg/kg) or physostigmine (0.01 and 0.025 mg/kg, but not 0.05 mg/kg). Combinations of the two drugs never improved active or passive avoidance performance more than drugs given separately. This indicates no advantage in combining nootropics and anticholinesterase inhibitors to improve learning and memory.

Animals↗

PubMed1992

Enhancement by oxiracetam of passive avoidance improvement induced by the presynaptic muscarinic antagonist secoverine in mice.

Post-trial administration of secoverine (0.5, 1 and 2.5 mg/kg), a presynaptic muscarinic blocker, improved retention in mice tested in a passive avoidance task. The nootropic drug oxiracetam (50 mg/kg), given before both acquisition and retention trial, had no effect alone, but significantly enhanced secoverine improving effects. Performance improvements were also found in combining ineffective doses of the two compounds. Even if not necessarily through a direct and specific action, oxiracetam might activate cholinergic function. Thus, performance improvements resulting from the combination of oxiracetam and secoverine may be due to a simultaneous activation of different cholinergic mechanisms.

Animals↗

PubMed1992

Choice behavior of fornix-damaged rats in radial maze error-free situations and subsequent learning.

Fornix-damaged, sham-operated, and control rats were placed in a radial eight-arm maze for fixed series of runs with either a 0% or a 100% reinforcement schedule in order to study their choice behavior independently from any learning problem. Subsequently, the ability to learn the radial maze task was examined as a function of the exploratory patterns developed in each error-free situation. The results showed that the continuous absence or presence of food in the radial maze induced two distinct models of exploration in sham-operated and control rats: choice alternation in the absence of food and perseveration in the presence of food. Conversely, this dichotomy did not occur in fornix-damaged rats that run approximately the same number of paths in both error-free situations, but made fewer different path choices in the 0% reinforcement condition and more different path choices in the 100% reinforcement condition than controls. When submitted to the radial maze task, a positive transfer was observed in all groups from the error-free situation in which the rats run more different paths: from the 0% reinforcement situation for controls and from the 100% reinforcement situation for the lesioned rats. These data indicate that damaging the septo-hippocampal pathway modifies spontaneous choice behavior through a different response to specific reinforcement programs but does not prevent the memorization and the transfer of information from error-free to learning situations.

Animals↗

PubMed1992

Genotype-dependent involvement of limbic areas in spatial learning and postlesion recovery.

Male C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampal, amygdaloid, or sham lesions were tested in a radial eight-arm maze 1 or 4 weeks after surgery. The results show that the effect of the lesions varied according to the performance level of the strain considered. In the high-learner C57 strain, the two lesions impaired acquisition at both postlesion intervals. Conversely, in the low-learner DBA strain, only hippocampal lesions impaired acquisition 1 week but not 4 weeks after lesioning. It is hypothesized that if more limbic areas are involved in controlling spatial learning in C57 mice, these structures could be processing distinct but complementary memory attributes, thus contributing to a high baseline performance. This, however, also entails an increased sensitivity of C57 performance to brain damage with reduced possibilities of long-term recovery.

Amygdala↗

PubMed1991

Clonidine reverses spatial learning deficits and reinstates theta frequencies in rats with partial fornix section.

Rats received knife-cuts to the dorsal fornix or sham-operations. Half of the animals from each group were injected with clonidine (0.01 mg/kg) and the others with saline before each daily trail of a 10-trial radial 8-arm maze task. The number of choices before the first repetition and the run time were used as performance indices. Lesioned rats were significantly impaired in the acquisition of this task. Clonidine-treated rats, lesioned or not, had an acquisition profile indistinguishable from that of sham-operated saline-injected rats, in spite of their increased run time. When tested one week after the last learning trial in a no-drug condition, lesioned rats treated with clonidine throughout learning maintained a high level of performance during the 5-day retraining phase. A parallel analysis of theta rhythms recorded in an independent group of rats placed in equivalent treatment and/or lesion conditions was then performed. Preoperatively, clonidine injections decreased theta frequency during both alert immobility and movement. Partial fornix lesions produced an increase in theta frequency. Finally, clonidine in fornix-damaged rats decreased theta frequency, thus reinstating the postoperative values at a level statistically no different from that recorded preoperatively. The role of clonidine in restoring the function of the septo-hippocampal input in partially fornix-damaged rats through a noradrenergic modulation of hippocampal acetylcholine release is discussed.

Acetylcholinesterase↗

PubMed1991

Spatial learning in two inbred strains of mice: genotype-dependent effect of amygdaloid and hippocampal lesions.

Spatial learning performance and maze-running strategies were estimated in two inbred strains of mice, C57BL/6 and DBA/2, submitted to an 8-arm radial maze task. Subsequently the genotype-dependent effect of hippocampus and amygdala on the mastering of this task was examined as a function of the different acquisition model provided by each strain. The results firstly show that unoperated C57BL/6 mice reach a higher level of performance and develop a stronger preference for adjacent arms - 45 degrees angle - turns than unoperated DBA/2 mice. In the high learner C57BL/6 strain, both hippocampal and amygdaloid lesions impair performance and modify maze-running strategies. With practice, however, the difference between amygdala-lesioned mice and controls disappears while that between hippocampus-lesioned mice and controls persists. Conversely, in the low learner DBA/2 strain, hippocampal lesions have a negative effect on a single parameter of performance, while amygdaloid lesions only affect maze-running strategies. Taken together, these results confirm the specific control exerted by the hippocampus on spatial learning. Moreover, they suggest that the amygdala can parallel the role of the hippocampus as far as the baseline level of performance of the strain considered is high.

Amygdala↗

PubMed1991

Amygdala and dorsal hippocampus lesions block the effects of GABAergic drugs on memory storage.

These experiments examined the effects of posttraining systemic administration of the GABAergic agonist muscimol and the GABAergic antagonist bicuculline on retention in mice with bilateral lesions of the amygdala, dorsal hippocampus or caudate nucleus. Unoperated male CD1 mice and mice with either sham lesions or electrolytically induced lesions of these 3 brain regions were trained in a one-trial inhibitory avoidance task and, immediately after training, received i.p. injections of either muscimol, (1.0, 2.0 or 3.0 mg/kg), bicuculline, (0.25, 0.5 or 1.0 mg/kg), or control solutions. Retention was tested 24 h after training. Lesions of the 3 brain regions produced comparable impairment of retention. In the unoperated controls and sham controls muscimol and bicuculline produced dose-dependent impairment and enhancement, respectively, of retention. The drug effects on retention were blocked by lesions of the amygdala and hippocampus, but were not blocked by lesions of the caudate nucleus. These findings are consistent with other recent evidence suggesting that the amygdala and hippocampus are involved in mediating posttraining neuromodulatory influences on memory storage.

Amygdala↗

PubMed1991

Prenatal exposure to gamma/neutron irradiation: sensorimotor alterations and paradoxical effects on learning.

The effects of prenatal exposure on gamma/neutron radiations (0.5 Gy at about the 18th day of fetal life) were studied in a hybrid strain of mice (DBA/Cne males x C57BL/Cne females). During ontogeny, measurements of sensorimotor reflexes revealed in prenatally irradiated mice 1) a delay in sensorial development, 2) deficits in tests involving body motor control, and 3) a reduction of both motility and locomotor activity scores. In adulthood, the behaviour of prenatally irradiated and control mice was examined in the open field test and in reactivity to novelty. Moreover, their learning performance was compared in several situations. The results show that, in the open field test, only rearings were more frequent in irradiated mice. In the presence of a novel object, significant sex x treatment interactions were observed since ambulation and leaning against the novel object increased in irradiated females but decreased in irradiated males. Finally, when submitted to different learning tasks, irradiated mice were impaired in the radial maze, but paradoxically exhibited higher avoidance scores than control mice, possibly because of their low pain thresholds. Taken together, these observations indicate that late prenatal gamma/neutron irradiation induces long lasting alterations at the sensorimotor level which, in turn, can influence learning abilities of adult mice.

Animals↗

PubMed1991

Open field behaviours and spatial learning performance in C57BL/6 mice: early stage effects of chronic GM1 ganglioside administration.

One month intact C57BL/6 mice were treated with GM1 ganglioside for 3 consecutive weeks. At 2 months of age, treated and control mice were observed in the open-field situation and tested for spatial learning in a radial eight-arm maze. The results showed that, in the open-field, treated mice displayed less freezing but more rearing behavior than control animals. In the radial maze, GM1-treated mice made more correct path choices before the first error within each trial than control mice. However, this improvement was limited to the first stage of training. These results suggest an early stimulating effect of the GM1 ganglioside treatment which could facilitate adaptive reactions to new situations.

Animals↗

PubMed1991

Effects of oxiracetam-nicotine combinations on active and passive avoidance learning in mice.

Tested alone, in CD-1 mice, the nootropic drug oxiracetam (50 mg/kg) improved learning in a multitrial active avoidance task (shuttle-box), but did not affect one-trial passive avoidance acquisition. Nicotine, which was ineffective at the dose of 0.25 mg/kg, improved both active and passive avoidance at the dose of 0.5 mg/kg; 1 mg/kg nicotine still exerted facilitating effects on passive avoidance, but slightly depressed shuttle-box performance. Combinations of oxiracetam and nicotine improved passive avoidance more than either drug given separately. In the active avoidance task, a combination of oxiracetam with the lower dose of nicotine exerted improving effects never observed with nicotine alone, even at higher doses. The nootropic drug also prevented the slight depressant action exerted by 1 mg/kg nicotine. Thus, contrary to what was previously supposed, at least in mice subjected to shuttle-box avoidance training, nicotinic activation does not appear as the main neurochemical mechanism involved in the action of oxiracetam. Perhaps, oxiracetam and nicotine activate different types of cholinergic mechanisms, but it cannot be excluded that other neurotransmitters, particularly catecholamines, may be involved in the avoidance facilitating effects produced by nicotine and by combinations of the two drugs.

Animals↗

PubMed1990

Chronic administration of phosphatidylserine during ontogeny enhances subject-environment interactions and radial maze performance in C57BL/6 mice.

A longitudinal behavioral study was performed in mice exposed to the bovine brain phospholipid phosphatidylserine (BC-PS) from birth until sixty days. Examination of treated and control pups revealed no effect of the treatment on body weight nor on sensorimotor reflexes. At one and two months of age, when placed in an open field and, particularly, in the presence of a novel object, treated mice were found more interactive with their environment than control mice. Finally, when submitted to a radial eight-arm maze problem, choice accuracy was higher and maze-running strategies more adaptive in treated than in control adult mice. These results suggest a stimulating effect of the treatment on subject-environment interactions during ontogeny underlying improved cognitive abilities in adulthood.

Aging↗

PubMed1990

Oxiracetam prevents mecamylamine-induced impairment of active, but not passive, avoidance learning in mice.

The nicotinic antagonist mecamylamine (2.5 and 5 mg/kg/IP) depressed both active (shuttle-box) and passive (step-through) avoidance learning in mice of the DBA/2 strain. The nootropic drug oxiracetam (50 and 100 mg/kg/IP) improved acquisition in the multitrial active avoidance test, but had no effect on one-trial passive avoidance learning. When the two drugs were combined, oxiracetam did not counteract mecamylamine-induced impairment of passive avoidance learning, even if it maintained a facilitating action on shuttle-box avoidance acquisition in mice receiving the nicotinic receptor blocker. Prevention of mecamylamine-induced shuttle-box avoidance depression by oxiracetam indicates that central nicotinic mechanisms are probably involved in the improving effects exerted by nootropic drugs on learning.

Animals↗

PubMed1989

Blocking of morphine-induced locomotor hyperactivity by amygdaloid lesions in C57BL/6 mice.

Bilateral lesions of the amygdaloid complex in C57BL/6 mice prevented the occurrence of morphine-induced hypermotility (running fit). This effect, that was different from that observed after hippocampal lesions but similar to that observed after caudate lesions, confirms the role of the basal ganglia catecholaminergic system in the development of the motor stimulation consecutive to the administration of this opiate receptor agonist.

Amygdala↗

PubMed1988

Prenatal antagonism of stress by naltrexone administration: early and long-lasting effects on emotional behaviors in mice.

The effects of prenatal exposure to stress and to naltrexone on emotional behaviors were studied in CD1 mice during ontogeny and in the adulthood. During ontogeny (a) lower body weights were initially found in pups born by mothers injected with naltrexone; (b) treatments did not affect sensory motor development except in the case of the cliff aversion reflex which occurred earlier in pups prenatally exposed to stress; (c) measures of ultrasonic vocalizations in stressful context showed that the amount of vocalizations emitted by pups born by stressed mothers was significantly higher than that emitted by pups born by naltrexone injected and control mothers (d) an examination of mother-offspring interactions on the very first day of observation indicated a consistent trend in stressed mothers to be more responsive to their pups. In adulthood, ultrasonic calls in courtship after short and long periods of isolation showed a time-dependent decrease of vocalizations in males prenatally exposed to naltrexone. These results indicate that the modifications of emotionality evident during early development are directly related to the reactivity of the mothers to the experimental treatments.

Animals↗

PubMed1988

Enhancement of radial maze performances in CD1 mice after prenatal exposure to oxiracetam: possible role of sustained investigative responses developed during ontogeny.

A longitudinal study aimed at analyzing the behavioral effects of prenatal exposure to the nootropic compound oxiracetam was carried out in CD1 mice. Two groups of females were injected either with oxiracetam or saline from the beginning of pregnancy until parturition. Examination of pups from birth until the first month of age revealed no-influence of the treatment on litter size, body weights, sensory motor reflexes and motility. When placed in the open field at one month of age, mice born by mothers exposed to oxiracetam displayed more self grooming and spent less time in freezing than control mice. Prenatally treated mice were then found more interactive with their environment since the introduction of a novel object in the open field was followed by increased ambulation and higher sniffing object and rearing object scores. At three months of age, mice from both groups were tested in a radial six-arm maze task. Choice accuracy was significantly higher in prenatally treated mice which also tended to optimize their exploratory sequences by frequently running the maze in a clock-wise fashion. These results suggest that the better learning performances observed in the experimental group could be viewed as a consequence of an enhanced cognitive development based upon the higher rate of interactions with the environment shown by prenatally treated mice during ontogeny.

Animals↗