Effect of exogenous retinoic acid on tooth movement and periodontium healing following tooth extraction in a rat model.

OBJECTIVES: To evaluate the effect of isotretinoin on orthodontic tooth movement (OTM) and wound healing following exodontia. SETTING AND SAMPLE POPULATION: Sixteen 40-day-old male Wistar rats were divided into two groups: (a) OTM and (b) tooth extraction (TE) of the upper 1st molar and OTM. The experimental animals were treated with isotretinoin (7.5 mg/kg) and the control animals with oil solution for 37 days. MATERIALS AND METHODS: The OTM and bone volume were evaluated by the micro-CT and the periodontium healing was assessed by immunohistochemistry for VEGF-C, COX-2 and IL-1ß. RESULTS: The animals of both groups submitted to the TE showed a statistically significant decrease in the bone volume percentage and increase in OTM. No significant difference of OTM and bone volume was observed between the control and experimental group. However, the alveolar bone of the isotretinoin group revealed more medullary spaces with inflammatory, hematopoietic cells, blood vessels and intense immunolabeling for VEGF-C. This group also showed faster gingival regeneration. No significant difference was observed in the COX-2 and IL-1ß labelings following TE between both groups. CONCLUSION: The isotretinoin did not affect the OTM nor did it cause an alteration in maxillary bone volume. This exogenous acid may contribute to the acceleration of gingival healing.

Could transient hypoxia be associated with rhythmic masticatory muscle activity in sleep bruxism in the absence of sleep-disordered breathing? A preliminary report.

Sleep bruxism (SB) is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth during sleep. Sleep bruxism activity is characterised by rhythmic masticatory muscle activity (RMMA). Many but not all RMMA episodes are associated with sleep arousal. The aim of this study was to evaluate whether transient oxygen saturation level change can be temporally associated with genesis of RMMA/SB. Sleep laboratory or home recordings data from 22 SB (tooth grinding history in the absence of reported sleep-disordered breathing) and healthy subjects were analysed. A total of 143 RMMA/SB episodes were classified in four categories: (i) no arousal + no body movement; (ii) arousal + no body movement; (iii) no arousal + body movement; (iv) arousal + body movement. Blood oxygen levels (SaO2 ) were assessed from finger oximetry signal at the baseline (before RMMA), and during RMMA. Significant variation in SaO2 over time (P = 0·001) was found after RMMA onset (+7 to +9 s). No difference between categories (P = 0·91) and no interaction between categories and SaO2 variation over time (P = 0·10) were observed. SaO2 of six of 22 subjects (27%) remained equal or slight increase after the RMMA/SB onset (+8 s) compared to baseline; 10 subjects (45%) slightly decreased (drop 0·01-1%) and the remaining (27%) decreased between 1% and 2%. These preliminary findings suggest that a subgroup of SB subjects had (i) a minor transient hypoxia potentially associated with the onset of RMMA episodes, and this (ii) independently of concomitant sleep arousal or body movements.

Airway Phenotypes and Nocturnal Wearing of Dentures in Elders with Sleep Apnea.

The objective of this study was to examine to what extent the anatomic characteristics of the upper airway can influence the effect of nocturnal wearing of dentures on the sleep of edentulous elders with untreated sleep apnea. This study used the data from a randomized crossover clinical trial and an exploratory approach to address its objectives. Cone beam computed tomography scans of 65 edentulous individuals (female, n = 37; male, n = 28; mean ± SD age, 74.54 ± 6.42 y) with untreated obstructive sleep apnea (OSA) were used to identify anatomic variables. Polysomnography data were collected by means of one portable overnight recording. The respiratory variable values, including apnea-hypopnea index (AHI), with and without denture worn during sleep were used to calculate the change. Statistical analyses included multiple linear regressions, cluster analysis, and binary logistic regressions. A receiver operator characteristic curve was used to illustrate the accuracy of the statistical model. The regression model explained 15.8% (R2) of AHI change. An increase in the lateral dimension of the minimum cross-sectional area was associated with a decrease in AHI, oxygen desaturation index, and respiratory arousal index changes (P ≤ 0.041). Furthermore, an increase in the length of the hypopharynx was associated with an increase in AHI and oxygen desaturation index changes (P ≤ 0.027). An increase in the lateral dimension of the minimum cross-sectional area of the upper airway was associated with a decreased likelihood of being in the group having a worsened AHI (odds ratio = 0.85; 95% CI, 0.76 to 0.95; P = 0.006). An increase in the length of the oropharynx was associated with an increased likelihood of having increased AHI (odds ratio = 1.10; 95% CI, 1.01 to 1.20; P = 0.026). The nocturnal aggravation of respiratory variables in edentulous individuals with OSA who wear dentures at night can be linked to certain anatomic characteristics of the upper airway. Replication of these findings may open novel avenues for personalized advice regarding nocturnal wearing of dentures in edentulous individuals with OSA (ClinicalTrials.gov: NCT01868295).

Is oral health-related quality of life stable following rehabilitation with mandibular two-implant overdentures?

OBJECTIVES: The superiority of mandibular two-implant overdentures (IODs) over conventional complete dentures (CDs) in terms of quality of life is still questioned. Furthermore, the stability and magnitude of the treatment effect over time remain uncertain. This follow-up study aimed to determine the stability and magnitude of the effect of IODs on oral health-related quality of life (OHRQoL). MATERIAL AND METHODS: 172 participants (mean age 71 ± 4.5 years) randomly received CDs or IODs, both opposed by conventional maxillary dentures. OHRQoL was measured using the Oral Health Impact Profile (OHIP-20) at baseline, 1 and 2 years post-treatment. Repeated measures ANOVAs were conducted to assess the effects of time and treatment on the total OHIP and its individual domain scores. RESULTS: A statistically significant improvement in OHRQoL was seen for both treatment groups (P < 0.001). This improvement was maintained over the 2 year assessment. At both follow-ups, participants wearing IODs reported significantly better total OHIP scores than those wearing CDs (P < 0.001), with a 1.5 times larger magnitude of effect. In the CD group, baseline OHIP scores influenced the post-treatment scores (P < 0.001). This effect was not found in the IOD group. CONCLUSIONS: The effect of mandibular two-IODs on OHRQoL is stable over a 2-year period. The large magnitude of effect of this treatment supports its clinical significance.

Comparison of ambulatory and polysomnographic recording of jaw muscle activity during sleep in normal subjects.

Clinicians and investigators need a simple and reliable recording device to diagnose or monitor sleep bruxism (SB). The aim of this study was to compare recordings made with an ambulatory electromyographic telemetry recorder (TEL-EMG) with those made with standard sleep laboratory polysomnography with synchronised audio-visual recording (PSG-AV). Eight volunteer subjects without current history of tooth grinding spent one night in a sleep laboratory. Simultaneous bilateral masseter EMG recordings were made with a TEL-EMG and standard PSG. All types of oromotor activity and rhythmic masseter muscle activity (RMMA), typical of SB, were independently scored by two individuals. Correlation and intra-class coefficient (ICC) were estimated for scores on each system. The TEL-EMG was highly sensitive to detect RMMA (0·988), but with low positive predictive value (0·231) because of a high rate of oromotor activity detection (e.g. swallowing and scratching). Almost 72% of false-positive oromotor activity scored with the TEL-EMG occurred during the transient wake period of sleep. A non-significant correlation between recording systems was found (r = 0·49). Because of the high frequency of wake periods during sleep, ICC was low (0·47), and the removal of the influence of wake periods improved the detection reliability of the TEL-EMG (ICC = 0·88). The TEL-EMG is sensitive to detect RMMA in normal subjects. However, it obtained a high rate of false-positive detections because of the presence of frequent oromotor activities and transient wake periods of sleep. New algorithms are needed to improve the validity of TEL-EMG recordings.

Perceived sleep quality among edentulous elders.

BACKGROUND: Anatomical changes associated with edentulism are thought to disturb seniors' sleep. OBJECTIVES: (1) To determine sleep quality and daytime sleepiness of edentulous elders. (2) To examine the association between oral health-related quality of life and sleep quality. METHODS: Data were collected at a 1-year follow-up from 173 healthy edentulous elders who had participated in a randomised controlled trial and randomly received two types of mandibular prosthesis. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI, range 0-21), with higher scores indicating poorer sleep quality. The Epworth Sleepiness Scale (ESS) was used to measure the level of perceived daytime sleepiness, and scores ≥10 indicated sleepiness. RESULTS: The mean global PSQI and ESS scores were 4.7 ± 3.5 and 5.3 ± 3.9. There were no differences in sleep quality or sleepiness between those who wore their dentures at night and those who did not. Elders with frequent denture problems were sleepier during the day than those with fewer problems (p = 0.0034). General health (p = 0.02) and oral health-related quality of life (p = 0.001) are significant predictors of sleep quality. CONCLUSION: Healthy edentulous elders, independent of nocturnal wearing of their prosthesis, are good sleepers. Maintaining high oral health quality of life could contribute to better sleep.

Sleep bruxism and sleep arousal: an experimental challenge to assess the role of cyclic alternating pattern.

Rhythmic masticatory muscle activity (RMMA) is the characteristic electromyographic pattern of sleep bruxism (SB), a sleep-related motor disorder associated with sleep arousal. Sleep arousals are generally organised in a clustered mode known as the cyclic alternating pattern (CAP). CAP is the expression of sleep instability between sleep maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). This study aimed to investigate the role of sleep instability on RMMA/SB occurrence by analysing CAP and electroencephalographic (EEG) activities. The analysis was performed on the sleep recordings of 8 SB subjects and 8 controls who received sensory stimulations during sleep. Baseline and experimental nights were compared for sleep variables, CAP, and EEG spectral analyses using repeated measure ANOVAs. Overall, no differences in sleep variables and EEG spectra were found between SB subjects and controls. However, SB subjects had higher sleep instability (more phase A3) than controls (P= 0·05). The frequency of phase A3 was higher in the pre-REM sleep periods (P < 0·001), where peaks in RMMA/SB activity were also observed (P = 0·05). When sleep instability was experimentally increased by sensory stimuli, both groups showed an enhancement in EEG theta and alpha power (P = 0·04 and 0·02, respectively) and significant increases in sleep arousal and all CAP variables. No change in RMMA/SB index was found within either groups (RMMA/SB occurred in all SB subjects and only one control during the experimental night). These findings suggest that CAP phase A3 may act as a permissive window rather than a generator of RMMA/SB activity in predisposed individuals.

Oro-facial activities in sleep bruxism patients and in normal subjects: a controlled polygraphic and audio-video study.

To our knowledge, the large spectrum of sleep motor activities (SMA) present in the head and neck region has not yet been systematically estimated in normal and sleep bruxism (SB) subjects. We hypothesized that in the absence of audio-video signal recordings, normal and SB subjects would present a high level of SMA that might confound the scoring specificity of SB. A retrospective analysis of several SMA, including oro-facial activities (OFA) and rhythmic masticatory muscle activities (RMMA), was made from polygraphic and audio-video recordings of 21 normal subjects and 25 SB patients. Sleep motor activities were scored, blind to subject status, from the second night of sleep recordings. Discrimination of OFA included the following types of activities: lip sucking, head movements, chewing-like movements, swallowing, head rubbing and scratching, eye opening and blinking. These were differentiated from RMMA and tooth grinding. The frequency of SMA per hour of sleep was lower in normal subjects in comparison with SB patients (P < 0.001). Up to 85% of all SMA in normal subjects were related to OFA while 30% of SMA in SB patients were related to OFA scoring (P < 0.001). The frequency of RMMA was seven times higher in SB patients than in normal subjects (P < 0.001). Several SMA can be observed in normal and SB subjects. In the absence of audio-video signal recordings, the discrimination of various types of OFA is difficult to achieve and may lead to erroneous estimation of SB-related activities.

[Molecular and genetic aspects of idiopathic scoliosis. Blood test for idiopathic scoliosis]. / Molekulare und genetische Aspekte der idiopathischen Skoliose. Bluttest bei idiopathischer Skoliose.

Spinal deformities, and particularly scoliosis, are the most frequent forms of orthopedic deformities in children and adolescents. About 1-6% of the population has scoliosis. This disorder leads to severe spinal deformities and predominantly affects adolescent girls.Although the multifactorial origin of adolescent idiopathic scoliosis (AIS) is broadly recognized, the genetic causes of AIS are still largely unknown. Our previous studies suggested a generalized dysfunction of melatonin transduction (the hormone that is primarily produced in the brain and epiphysis). In the meantime we have demonstrated that such a defect of signal transduction is caused by chemical alterations, which inactivate the function of the inhibitory G protein-coupled melatonin receptors. This discovery has led to the development of the first blood test to detect children without symptoms who are at risk of developing scoliosis. Since a single function (cellular reaction to melatonin) is determined, the unique advantage of this test is that it can be performed without knowledge of mutations in defective genes that could provoke the onset of AIS.

Carious lesion management in children and adolescents by Australian dentists.

BACKGROUND: The management of carious lesions in children and adolescents can have lifelong implications for the patient. The aim of this study was to assess the decision-making process of dentists when managing carious lesions in children and adolescents. METHODS: Approximately, 11 000 dentists listed as members of the Australian Dental Association Inc. (ADA) and Australian and New Zealand Society of Paediatric Dentistry (ANZSPD) were emailed a link in April 2017 to a 19-question survey delivered by SurveyMonkey™. RESULTS: In this study, 887 responses were received. In 'enamel-limited' carious lesions, dentists intervened most frequently in primary tooth approximal (365, 41.1%), followed by permanent tooth occlusal (295, 33.3%) and approximal (244, 27.5%), and primary tooth occlusal (203, 22.9%) surface carious lesions. Age, university of graduation, practicing state, decade of graduation and frequency of treatment of children between 6 and 15 years were significant demographic factors influencing the restorative threshold. CONCLUSIONS: Australian dentists reported significant variation in their management of approximal and occlusal carious lesions in both primary and permanent teeth. A substantial proportion of respondents would intervene surgically on non-cavitated enamel-limited lesions.

Favoring trauma as an etiological factor in denture stomatitis.

The etiology of denture stomatitis remains controversial. Trauma due to unstable dentures has been suggested as an etiological factor. Therefore, we tested the hypothesis that the prevalence of denture stomatitis is reduced when mandibular dentures are stabilized by implants. Data were collected at a one-year follow-up from 173 edentulous elders who had randomly received mandibular implant overdentures or conventional dentures. The diagnosis of denture stomatitis was determined according to the Newton classification. Elders wearing conventional dentures were almost 5 times more likely to have denture stomatitis than those wearing mandibular two-implant overdentures (P < 0.0001, Fisher's exact test). Adjusted odds ratios showed that only the type of the prosthesis (AOR = 4.54, 95% CI 2.20 to 9.40) and nocturnal wear (AOR = 3.03, 95% CI 1.24 to 7.40) predict the frequency of denture stomatitis. Thus, implant overdentures may reduce oral mucosal trauma and control denture stomatitis.

Identification of a sleep bruxism subgroup with a higher risk of pain.

Sleep bruxism research diagnostic criteria (SB-RDC) have been applied since 1996. This study was performed to validate these criteria and to challenge the hypothesis that pain is associated with lower frequencies of orofacial activities. Polygraphic recordings were made of 100 individuals presenting with a clinical diagnosis of sleep bruxism and 43 control individuals. TwoStep Cluster analyses (SPSS) were performed with sleep bruxism variables to reveal groupings among sleep bruxers and control individuals. Participants completed questionnaires during screening, diagnosis, and recording sessions. Cluster analysis identified three subgroups of sleep bruxers. Interestingly, 45 of the 46 sleep bruxers with values below SB-RDC were classified in the low-frequency cluster. These individuals were more likely to complain of pain and fatigue of masticatory muscles than were the higher-frequency sleep bruxers (odds ratios > 3.9, p < 0.01). Sleep bruxers were distributed among three heterogeneous groups. Sleep bruxers with low frequencies of orofacial activities were more at risk of reporting pain.

Tooth Loss Increases the Risk of Diminished Cognitive Function: A Systematic Review and Meta-analysis.

Emerging evidence suggests that oral health is associated with cognitive function. This review aims to systematically assess this association in adult populations via prospective cohort study designs. Eligible study reports were identified by searching the MEDLINE (via Ovoid), EMBASE, PsycoINFO, and Cochrane Library databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with a random effects model. From 1,251 identified articles, 10 were included in the systematic review and 8 in the meta-analysis. Random effects analysis showed, with statistically low heterogeneity, that individuals with suboptimal dentition (<20 teeth) were at a 20% higher risk for developing cognitive decline (HR = 1.26, 95% CI = 1.14 to 1.40) and dementia (HR = 1.22, 95% CI = 1.04 to 1.43) than those with optimal dentition (≥20 teeth). Studies on the association between periodontal disease and cognitive status showed conflicting results. Within the limits of the quality of published evidence, this meta-analysis lends further support to the hypothesis that tooth loss is associated with an increased risk of cognitive impairment and dementia. Knowledge Transfer Statement: Based on the published literature, the results of this study show that the risk for cognitive impairment and dementia increases with loss of teeth. This information adds to the evidence showing links between oral and general health and suggests that oral health strategies aimed to preserve teeth may be important in reducing risk of systemic disease.

Behavioral evidence of depolarization block of dopamine neurons after chronic treatment with haloperidol and clozapine.

Electrophysiological studies have shown that chronic treatment with haloperidol causes depolarization block (DB) of dopamine cells in anesthetized and paralyzed rats. It has been proposed that the emergence of DB underlies the therapeutic and side effects of this drug. However, the relevance of DB to the clinical actions of haloperidol has been questioned on the grounds that chronic drug-induced DB has not yet been demonstrated in freely moving animals. In this study, responding for rewarding electrical brain stimulation was used to assess the occurrence of DB in rats chronically treated with haloperidol or clozapine. The time course of the effects of acute haloperidol (7.8-500 microg/kg) and clozapine (5-40 mg/kg) and of withdrawal from chronic drug treatment on reward and performance measures were also characterized. Haloperidol and clozapine dose-dependently attenuated reward and performance, haloperidol producing a predominant suppression of performance, and clozapine preferentially attenuating reward. Chronic (21 d) treatment with haloperidol (500 microg/kg) caused responding to cease in the six rats tested, and repeated injection with apomorphine restored the behavior in all of them; such an effect of apomorphine was observed in only two of six rats treated acutely with the same dose of haloperidol. Chronic treatment with clozapine (20 mg/kg) increased reward thresholds, an effect that was reversed by apomorphine in chronically, but not acutely, treated rats. The times at which chronic haloperidol-treated rats resumed responding was positively correlated with indices of behavioral supersensitivity after withdrawal, suggesting that the effect of apomorphine was not caused by direct stimulation of upregulated postsynaptic receptors. These findings constitute the first behavioral evidence of DB in unanesthetized, freely moving animals treated chronically with antipsychotics. They also demonstrate that the neural substrates mediating reward and performance are functionally independent and differentially sensitive to haloperidol and clozapine.

Evidence for a role of endogenous neurotensin in the initiation of amphetamine sensitization.

This study was aimed at testing the hypothesis that endogenous neurotensin plays a role in the initiation of sensitization to the locomotor activating effect of amphetamine. During an initial training phase, different groups of male rats were injected on four occasions (every second day: Days 1, 3, 5 and 7) with one of three doses (40, 80 or 160 microg/kg, ip) of the neurotensin antagonist, SR-48692, or its vehicle, followed 30 min later by amphetamine (1.5 mg/kg, ip), or saline. Ambulatory, non-ambulatory, and vertical movements were measured for 2 h in photocell cages immediately following the second injection. One week after the training phase, sensitivity to amphetamine (0.75 mg/kg, ip) was tested in all the rats (sensitization test). The results show that SR-48692, when given alone, produced levels of locomotor activity that were not statistically different from control. At the low dose, it potentiated amphetamine-induced ambulatory and non-ambulatory movements, an effect observed on Day 7 but not on Day 1. On the day of the sensitization test, rats pre-exposed to amphetamine alone displayed stronger ambulatory and non-ambulatory movements than vehicle pre-exposed rats, a sensitization effect that was attenuated and prevented by SR-48692 at 80 and 160 microg/kg, respectively. The present results demonstrate that activation of neurotensin receptors by endogenous neurotensin is required for the initiation of amphetamine sensitization. They provide additional evidence that an increase in central neurotensinergic neurotransmission may lead to a lasting increased sensitivity to psychostimulant drugs.

Cigarette smoking as a risk factor or an exacerbating factor for restless legs syndrome and sleep bruxism.

Cigarette smoking has been associated with sleep disturbances. However, little is known about how smoking affects restless legs syndrome (RLS) and sleep bruxism, two movement disorders associated with sleep. From a nationwide survey of 2,019 Canadian adults, we estimated the prevalence of smoking to be 36%. Although there was no difference between smokers and nonsmokers for RLS prevalence, almost twice as many smokers (12%) as nonsmokers (7%) were aware of experiencing sleep bruxism. The estimated risk of a smoker suffering from RLS was nonsignificant. On the other hand, the risk of a smoker grinding his or her teeth was moderate (odds ratio = 1.9). Analysis of sleep laboratory findings revealed no differences in motor RLS and periodic leg movements in sleep (PLMS) indices between smoking and nonsmoking patients; after adjustment for age, there were no differences in sleep efficiency, latency, number of awakenings, or the arousal index for the RLS/PLMS patients. Among those suffering from bruxism, smokers had more tooth-grinding episodes than did nonsmokers (35.0 vs. 7.0; p = 0.056); none of the sleep variables differentiated sleep bruxism smokers from nonsmokers. It appears that cigarette smoking does not influence RLS/PLMS, whereas the risk that smoking and tooth grinding are concomitant is moderate. Smoking was not significantly associated with more motor activity in RLS/PLMS, but more grinding was noted in sleep bruxism.

Effects of concomitant motor reactions on the measurement of rewarding efficacy of brain stimulation.

In self-stimulation behavior, the rate-frequency (R-F) function relates bar-pressing performance to the number of cathodal pulses of constant intensity, delivered in a train of fixed duration. The lateral position of the R-F function depends on the rewarding efficacy of the stimulation; a shift of the function toward larger pulse numbers after some experimental manipulation indicates a decrease in the efficacy of the stimulation. Because self-stimulation is often accompanied by stimulation-contingent motoric reactions, it is required to show that such reactions do not alter the estimates of rewarding efficacy of the stimulation. We describe an experiment in which the presence and severity of motoric reactions were controlled experimentally by simultaneous stimulation through a second electrode, located in a motoric brain region. Rats were implanted with one hypothalamic (LH) electrode (which elicited self-stimulation) and one reticular (RF) electrode (which elicited head and body movements). The rate-frequency function for each LH electrode was obtained under a single-pulse condition (LH electrode alone) and under a paired-pulse condition repeated three times, in which each LH pulse was accompanied by three different intensities of an RF pulse. Despite its severe effect on the slope and the asymptotic rate of R-F function, the interfering reaction failed to shift the R-F function to any significant degree. We concluded that these interfering reactions do not alter the estimates of neuronal density obtained through application of the curve-shift paradigm.

Psychostimulant-like effect of central microinjection of neurotensin on brain stimulation reward.

The curve shift method and the brain stimulation reward paradigm were used to dissociate reward and performance changes and determine whether unilateral ICV microinjection of neurotensin (3, 10, and 30 micrograms/10 microliters) produces neuroleptic- or psychostimulant-like effect on a dopamine-dependent behavior. At the highest dose tested, neurotensin potentiated brain stimulation reward, producing a significant time-dependent decrease in frequency threshold. Neurotensin also suppressed maximal rate of responding at every dose tested, suggesting that it was more effective at attenuating performance capability. These results suggest that a centrally acting neurotensin receptor agonist may specifically stimulate dopamine-dependent behaviors, producing psychostimulant-like effect that can be attenuated or masked by a suppression of performance capability.

A comparison of the effects of mesencephalic injections of neurotensin(1-13) and neuromedin N on brain electrical self-stimulation.

Neuromedin N (NM-N), a hexapeptide that shares a four amino acid C-terminal homology with the tridecapeptide, neurotensin (NT), has been suggested as a potential neurotransmitter or neuromodulator that could interact with the NT-sensitive receptors. In this experiment, we compared the effects of an equimolar concentration of NM-N and NT(1-13) injected in the ventral tegmental area (VTA) on brain electrical self-stimulation (SS), a behavior previously shown to be potentiated by VTA injections of NT(1-13). Rats implanted with a stimulating electrode in the mesencephalic central gray and a guide cannula in the VTA were trained to lever press to obtain rewarding electrical stimulations. Functions relating the rate of lever pressing to the stimulation frequency were determined, on separate daily tests, before and after the injection of 3 nmol of NM-N, NT(1-13), or an equal volume of saline vehicle. At this concentration, both NM-N and NT(1-13) produced a significant facilitation of SS when compared to saline vehicle, an effect that was not seen when the peptides were injected outside the VTA. The facilitation of SS by NM-N, however, was much weaker and of a shorter duration than the one produced by NT(1-13). The shorter time course and the weaker behavioral effect of NM-N compared to NT(1-13) are consistent with its lower potency at the NT receptor and its faster rate of enzymatic degradation in the VTA, and suggest that NM-N potentiated the reward-relevant neural signal by acting on mesencephalic NT receptors.

Behavioral determination of refractory periods of the brainstem substrates of self-stimulation.

The objective of this study was to estimate the refractory periods of the brainstem neurons responsible for self-stimulation behavior in the rat. In a first experiment, we tested the robustness of the double pulse technique used to estimate the refractory periods of reward-relevant neurons. We obtained estimates of the relative T-pulse effectiveness at a wide range of stimulation frequencies. The results of this experiment suggest that the refractory period estimates obtained with the behavioral version of the double pulse technique are not dependent on the arbitrary choice of the stimulation frequency. However, the use of stimulation frequencies higher than 100 Hz should preferably be avoided. In a second experiment, we applied the double pulse technique using C-pulse intensity higher than T-pulse intensity to estimate the refractory periods of the brainstem reward-relevant neurons. Using moveable electrodes, we tested 9 metencephalic and 7 mesencephalic sites in 4 animals. In the metencephalon, the most excitable reward-relevant neurons have absolute refractory periods of less than 0.6 and 0.8 ms and have a supernormal period that occurs at least between 5 and 10 ms after the initial excitation. The mesencephalic reward-relevant neurons were found to have more heterogeneous physiological characteristics. The most excitable cells in the mesencephalon have absolute refractory periods of less than 0.4 ms and have a supernormal period occurring as soon as 2.4 ms after the initial excitation. At some mesencephalic sites, we observed first an abrupt initial recovery followed by a plateau, followed by a renewed and continuous recovery, a pattern that was never observed in the metencephalon. The hypothesis of the contribution of two distinct sub-populations of reward-relevant neurons is proposed and the implication of monoaminergic pathways in reward is discussed.