[Profile of first year secondary school children involved in the anti-smoking prevention trial "PEPITES"]. / Les collégiens de 6e participant à l'essai de prévention du tabagisme en milieu scolaire en Essonne : « PEPITES ¼.

BACKGROUND: Many programs which aim to reduce tobacco consumption in young people are carried out in the school environment, addressing a "captive audience" and monitoring the actions over a period of several years. The approaches identified as promising involve putting in place a tobacco prevention program throughout the entire school years incorporated in the school program. Several studies showed that early initiation to psychoactive substances is a strong predictor of addiction. Considering the above points, an intervention trial on tobacco prevention covering the four years of secondary school (±11-15 years old) was implemented in the Essonne area, in France. METHOD: This study was based on a cluster randomized trial comparing three groups: two intervention groups and a control group. The present paper describes the school children (1st year in six secondary schools) included in the trial. It studies the national representativity of this population, the comparability between the control and intervention groups and the items link to tobacco initiation. RESULTS: When considering tobacco behavior in 2014, the included population was representative of the school children in 1st year of secondary school in France with 11.5% of tobacco initiation and 2.5% of regular smokers. The groups were comparable except for four items (family and friends smoking, only child, sensitive urban areas). With this knowledge on factors linked to smoking behaviors this population can be included in the trial analysis. CONCLUSION: The study of the included population will help to perform the trial analysis and authorize the transferability of the trial results if positive.

Learning and memory dissociation in rats with lesions to the subthalamic nucleus or to the dorsal striatum.

The striatum and the subthalamic nucleus (STN) are the two main cortical inputs to the basal ganglia. Both structures are involved in motor and cognitive functions, particularly executive functions, known to rely mainly on fronto-basal ganglia circuits. The present work investigated the respective role of the dorsal part of the striatum (dST) and the STN by studying their involvement in learning and memory processes in two separate experiments. In a first experiment, rats with lesions to the STN or to the dST were trained in a light-tone discrimination task. When the learning criterion was reached, rats were then trained to the reversed discrimination. In a second experiment, surgery was done when the learning criterion had been reached. Three weeks after surgery, animals were then subjected to two relearning sessions and then to either a reversal learning or a working memory task. When surgery was done before learning, dysfunction of the dorsal striatum induced slight difficulties in acquisition, whereas dysfunction of the STN induced no difficulties during the initial learning but induced a more rapid inhibition of responses to the first lever press following the presentation of the tone during the reversed discrimination. In the second experiment, dST-lesioned rats showed long-term memory deficit in contrast to STN-lesioned rats which showed no difficulties during relearning but deficits in working memory. These results indicate a clear dissociation in cognitive functions in which STN and dorsal striatum are involved, suggesting that the fronto-striatal circuit and the fronto-STN circuit support, at least in part, different cognitive functions.

Effects of medial prefrontal cortex and dorsal striatum lesions on retrieval processes in rats.

Exposure to training-related cues is known to reactivate associated memory and improves subsequent retention performance under various circumstances. The present studies investigated the neural basis of retrieval cue effects, by studying in two separate experiments, the involvement of the medial prefrontal cortex and of the dorsal striatum. Rats with lesions to the prelimbic-infralimbic cortex (PL-IL), to the anterior dorsal cingulate (ACd), and to the lateral and medial parts of the dorsal striatum (lDS and mDS) were first trained in a brightness discrimination avoidance task. One day later, rats were tested after being placed in the cueing box with either no training-related cue or with additional exposures to the light discriminative stimulus. None of the lesions affected the acquisition performance. During the retention test, control rats cued with the light in the box exhibited significantly better retention performance than those simply placed in the box, confirming our previous results. While mDS lesions did not modify effects of the retrieval cue, lDS as well as both PL-IL and ACd lesions blocked the facilitative effects of the discriminative stimulus. The present data indicate that ACd, PL-IL and lDS are involved in processes promoted by exposure to training cues, the nature of which are reviewed and discussed. This study in conjunction with previous ones suggests that retrieval cues activate several subcircuits mainly based on an amygdalo-prefrontal-striatum network. Activation of this network results in an improvement of the expression of the associated conditioned response, and may thus be viewed as increasing the efficacy of the retrieval processes.

Perseverative behavior underlying attentional set-shifting deficits in rats chronically treated with the neurotoxin 3-nitropropionic acid.

Huntington's disease (HD) is generally considered a prototypic motor disorder, but cognitive deficits are also prominent features of the disease. Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP) has been proposed to be a phenotypic model of HD in rats and nonhuman primates. In this study, we investigated the effect of 5 days continuous subcutaneous infusion of 3NP on motor and cognitive abilities in Lewis rats. Intoxicated animals developed a motor syndrome consisting of bradykinesia as well as gait abnormalities and dystonic hindlimbs. Results from learning tasks showed that these rats: (1) did not exhibit learning deficits per se in our discrimination task but showed impairments in inhibiting behavioral responses when a transfer of learning (to new stimuli) or a transfer of response (new position of the lever) was required; (2) showed a marked tendency to persevere in choosing the compartment they previously visited in a T maze, thus leading to a clear retardation in learning a reinforced alternation task; and (3) did not show any memory deficit when a delay was introduced. Six months later, histological analyses showed severe neurodegeneration within the lateral striatum accompanied by apparent cell loss in the ventral pallidum and entopedoncular nucleus. We suggest that the 3NP rat model of basal ganglia neurodegeneration may provide a useful model for studying certain fundamental aspects of the physiopathology of HD and for evaluating the functional efficacy of new therapeutic strategies.

Correlations between activity of pallidal neurons and motor parameters.

The relationships between the activity of 87 pallidal neurons and parameters characterizing motor performance were analysed quantitatively in six unrestrained cats performing a forelimb flexion movement controlled by a reaction-time paradigm. Three motor variables were considered: the static force exerted when the trigger stimulus occurred, the latency of the force change initiating the liver-release movement and the velocity of the force change. For all the cats, the latency of the change in force was the prevalent parameter in determining the movement onset occurrence. The single-unit activity was quantified on a trial-by-trial basis by measuring the mean firing rate in windows of fixed duration. Both normal (total) and partial linear correlation coefficients were used. Partial correlation coefficients were calculated between the mean firing rate during selected windows and each of the motor parameters. A total of 17% and 9% of all partial correlation coefficients tested (n = 1566) was found to be significantly different from zero, respectively with p < 0.05 and p < 0.01. The mean percentages of explained variation, measured by the square of the correlation coefficient, were 17% (p < 0.05) and 21% (p < 0.01). The 46 pallidal neurons presenting an increase in discharge after the trigger stimulus could be classified in homogeneous subgroups with respect to the signs of the correlations. Representations of the motor programme underlying reaction-time performance evidenced at the pallidal level further substantiate a specific involvement of the basal ganglia in the latency of motor triggering.

Activity of neurons of the subthalamic nucleus in relation to motor performance in the cat.

The activity of subthalamic nucleus neurons related to motor performance was studied in three unrestrained cats operantly conditioned to perform a lever-release movement. The movement was initiated either rapidly after the trigger stimulus (a brief sound) in a simple reaction-time paradigm or after a delay in trials identified by a tone cue. These paradigms were randomly presented. The activity of 171 neurons was recorded in the contralateral and in the ipsilateral subthalamic nucleus, with respect to the performing limb. The mean spontaneous activity of cells in the ipsilateral side (18.5 +/- 13.8 imp/s, mean +/- SD) was higher than that in the contralateral side (8.5 +/- 8.1 imp/s). A total of 145 cells (85%) presented significant changes in activity in relation to the lever-release movement (task-related cells). The remaining 26 cells were either related to other events of the task (n = 15; lever-press or reinforcement occurrence) or not related at all to the task performance (n = 11). The majority of changes of activity of task-related cells were initial increases in discharge, which started on average, 127 ms before movement onset and lasted several hundreds of milliseconds. These increases in discharge were more frequent in the contralateral side (75 of 80 task-related cells, 94%) than in the ipsilateral side (43 of 65 task-related cells, 66%). The changes in activity, either increases or decreases, occurred early after the trigger stimulus, since 62% of them had a latency of less than 100 ms. Although the mean latency of initial increases was rather similar in both sides (97 ms contralateral versus 104 ms ipsilateral), the contralateral side was characterized by a high proportion of very early responses (less than 20 ms). For most neurons, the early changes in activity described above were absent after the trigger stimulus in the delayed condition. For certain neurons, the changes in activity prior to movement were different in reaction-time condition and in delayed condition, showing that the pattern of activity preceding movement might depend on the temporal requirements for motor initiation. The results suggest that a significant proportion of subthalamic cells are involved in the preparation and the initiation phases of the lever-release movement studied, although other hypotheses (e.g. stimulus-related responses) cannot be definitely ruled out. The timings and patterns of the changes in activity observed in the subthalamic nucleus in the present study, and in the pallidal complex previously, cannot be explained easily by the classical scheme where the external pallidum inhibits the subthalamic nucleus. The results suggest rather that the subthalamic nucleus, driven by a yet-to-be-determined excitatory input, exerts an excitatory influence on the pallidum and plays a crucial role in the control of the basal ganglia output neurons.

The role of putamen and pallidum in motor initiation in the cat. I. Timing of movement-related single-unit activity.

The participation of basal ganglia in motor initiation was studied in six cats operantly trained to perform a ballistic flexion movement, triggered after a brief sound in a simple reaction time condition or delayed after the same sound in the presence of a tone cue. The activity of 356 neurons was recorded in the putamen and in the pallidum (globus pallidus and entopeduncular nucleus). A total of 19.4% of the neurons were not related to the conditioned flexion movement: they were either unrelated to the task (10.1%) or related to other periods of the motor performance such as trial beginning or reward delivery (9.3%). About 60% of the remaining neurons--defined as task-related--exhibited changes in firing rate that occurred, in the reaction time condition, less than 100 ms after the go signal and therefore began prior to movement onset. For most neurons, in the delayed condition, these early changes were absent, suggesting that their occurrence in the reaction time condition was not a sensory response but rather was related to the movement initiation. In addition, for many neurons these changes shifted in time, remaining time-locked to the movement. Correlations between these early changes in activity and motor parameters were demonstrated, suggesting that these changes were movement-related. For most neurons the firing levels observed during intertrial intervals and during foreperiod were similar. The mean discharge rate during the foreperiod was 19.2 impulses/s. Three patterns of activity were observed before movement: increases in discharge rate (61% of task-related neurons), transient decreases followed by increases (11%), or prolonged decreases (28%). Only minor differences were found between the characteristics of the populations of neurons recorded in the three sites under study: on average the neurons recorded in the globus pallidus were more active than the neurons recorded in the putamen or in the entopeduncular nucleus. The fact that, for certain neurons, the changes of activity prior to movement were different in reaction time condition and in delayed condition showed that the pattern of activity preceding movement might depend on the temporal requirements for motor initiation. Taken together with the motor effects obtained in the same task following GABA-receptor activation with muscimol microinjections in these structures, the present results suggest that putamen and pallidal neurons participate in the initiation of the conditioned movement under study.