Negative online reviews of orthodontists: Content analysis of complaints posted by dissatisfied patients.

INTRODUCTION: Patients may express views about their orthodontic care by posting publicly available reviews on the Internet. This study analyzed online reviews of orthodontists with an emphasis on the types and frequency of complaints expressed in negative reviews. METHODS: A random sample of 10.6% of the American Association of Orthodontists membership was evaluated to identify members practicing in a North American office that is limited to orthodontics and has an online presence. Information regarding those orthodontists and their offices was collected. For offices with Google and/or Yelp reviews, all negative (1- or 2-star) reviews were saved for content analysis. If an office posted a response to a negative review, those responses were also collected for analysis. RESULTS: Of the 807 eligible orthodontists, 92.4% had reviews on Google and/or Yelp. Average ratings of orthodontists were very positive (ie, 4- and 5-star reviews constituted >97% of Google reviews and >88% of Yelp reviews), yielding an average orthodontist rating of 4.72 on Google and 4.42 on Yelp. However, approximately half of those orthodontists (50.9%) also had at least 1 negative review. The 3 most frequently mentioned categories of complaints were regarding quality of care and/or service, interpersonal interactions, and money and/or financial issues. An analysis of the specific kinds of complaints is described. Orthodontists posting responses to negative reviews had significantly better average ratings than those who did not, but this association does not demonstrate a causal relationship. CONCLUSIONS: Understanding the complaints orthodontic patients express in online reviews may suggest strategies to improve patient satisfaction and an orthodontist's online reputation.

Individual differences in biological regulation: Predicting vulnerability to drug addiction, obesity, and other dysregulatory disorders.

Physiological regulation is so fundamental to survival that natural selection has greatly favored the evolution of robust regulatory systems that use both reactive and preemptive responses to mitigate the disruptive impact of biological and environmental challenges on physiological function. In good health, robust regulatory systems provide little insight into the typically hidden complex array of sensor-effector interactions that accomplish successful regulation. Numerous health disorders have been traced to defective regulatory mechanisms, and generations of scientists have worked to discover ways to correct these defects and restore normal physiological function. Despite progress, numerous chronic health disorders remain resistant to treatment, and indeed for some disorders the incidence is increasing. We propose that an individual's susceptibility to acquire certain persistent dysregulatory disorders can be traced to interindividual variation in how that individual's regulatory system responds to challenges. Preexisting reliable individual differences among regulatory systems are typically unrecognized until appropriate regulatory challenges (e.g., exposure to a drug of abuse) lead to dysregulation (e.g., drug addiction). Specific characteristics of an individual's regulatory responsiveness may include etiological factors that participate in the acquisition, escalation and maintenance of health disorders characterized by dysregulation. By appropriately challenging a healthy individual's regulatory systems to identify its underlying characteristics, it is possible to ascertain whether an individual has an elevated risk for acquiring a dysregulated health condition and thereby enable strategies designed to prevent, rather than treat, the condition. This model is applied to drug addiction, and in addition we relate this approach to other dysregulated conditions such as obesity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Mouthguards during orthodontic treatment: Perspectives of orthodontists and a survey of orthodontic patients playing school-sponsored basketball and football.

INTRODUCTION: The objectives of this research were to identify the beliefs and practices of orthodontists about mouthguard use in orthodontic patients and to survey orthodontic patients currently playing school-sponsored basketball and/or football about mouthguards. METHODS: Fifteen orthodontists were interviewed about mouthguard use in their patients. Patients (aged 11-18 years) playing organized school basketball (n = 53) or football (n = 22) from 13 of those 15 orthodontic practices participated in an online survey about mouthguards. RESULTS: Approximately half of the orthodontists interviewed had initiated discussions about mouthguards with their patients. Although boil-and-bite mouthguards were recommended most often by orthodontists with only a single orthodontist recommending a stock type, stock was the most commonly used type (football [59%], basketball [50%]) followed by boil-and-bite (football [27%], basketball [35%]). Only 2 of the 75 patients surveyed (<3%) reported using a custom mouthguard. All football players reported using a mouthguard, as mandated by this sport. Basketball does not mandate mouthguard use, and only 38% of basketball players reported wearing one. Players who used mouthguards cited forgetting as the most frequent reason for not always using one. A greater percentage of football (91%) than basketball (32%) players reported that their coach recommended a mouthguard (P <0.001). CONCLUSIONS: Orthodontists differ in how they approach mouthguard use by their patients, which likely reflects a lack of evidence-based guidelines. The beliefs, recommendations, and practices of orthodontists concerning mouthguard use and the use of mouthguards by orthodontic patients are discussed. Research directions to improve mouthguard use are suggested.

Reliability of the conditioned pain modulation paradigm across three anatomical sites.

Background and aims Conditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS (pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand. Methods Sixty healthy participants aged 18-65 were tested by the same examiner on 3 separate days, with an interval of 2-7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability. Results PPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants. Discussion The CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats.

BACKGROUND: Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. METHODS: This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C-38°C) to assess each adapted group's thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. RESULTS: In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. CONCLUSIONS: Acquired N2O hyperthermia in rats is remarkably robust, and occurs even despite the availability of ambient temperatures that might fully counter the hyperthermia. Increased locomotion in the gradient may contribute to hyperthermia. Our data are consistent with an allostatic dis-coordination of autonomic and behavioral thermoregulatory mechanisms during drug administration. Our results have implications for research on N2O abuse as well as research on the role of allostasis in drug addiction.

Plasma corticosterone, epinephrine, and norepinephrine levels increase during administration of nitrous oxide in rats.

Nitrous oxide (N2O) is a gaseous drug with abuse potential. Despite its common clinical use, little is known about whether N2O administration activates the HPA axis and/or the sympathetic adrenomedullary system. The goal of this study was to determine whether 60% N2O alters plasma concentrations of corticosterone (CORT), epinephrine (EPI), and norepinephrine (NE) in male Long-Evans rats. A gas-tight swivel assembly in the lid of a gas administration chamber allowed the remote collection of blood samples from an indwelling jugular vein catheter at four time-points: baseline and at 30, 60, and 120 min during a two-hour administration of 60% N2O. Relative to baseline, plasma CORT (n = 9) was significantly elevated at all three time-points during N2O inhalation (mixed model analysis, p = .001) and plasma EPI and NE levels were each significantly elevated (n = 8, p ≤ .001) at the 30 min assessment. EPI then declined and did not differ from baseline at the 60 and 120 min assessments (p > .05) whereas NE remained elevated (120 min, p = .001). Administration of 60% N2O increases circulating CORT, EPI, and NE, supporting N2O as a physiological stressor. An N2O-induced increase in CORT is consistent with the observation that addictive drugs typically activate the HPA axis causing increased plasma levels of glucocorticoids. Allostatic models of drug addiction typically involve stress systems and the possible role of stress hormones in N2O-induced allostatic dysregulation is discussed.

Felis Punctatis: Cat Claw-induced Punctures.

Animal-induced conditions in humans predominantly present as infectious zoonoses. However, trauma-associated injuries from the teeth or claws can also occur. Several zoonotic infections can be transmitted by cats, a common household pet, to their owners. The clinical features of a woman who developed multiple sites of trauma-induced cutaneous punctures from her cat's paws while it was kneading on her clothes-covered abdomen are described. The repetitive insertion and withdrawal of the sharp tips of the cat's claws created distinctive groups of erythematous punctures on the patient's skin. We suggest that Latin nomenclature be used to designate the name for this claw-induced dermatosis that includes not only the causative animal (felis for cat) but also a descriptive term for the skin lesions (punctatis for punctures): felis punctatis.

Physiological Regulation: How It Really Works.

Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.

Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.

Initial administration of ≥60% nitrous oxide (N2O) to rats promotes hypothermia primarily by increasing whole-body heat loss. We hypothesized that the drug promotes heat loss via the tail and might initially inhibit thermogenesis via brown adipose tissue (BAT), major organs of thermoregulation in rodents. Following repeated administrations, N2O inhalation evokes hyperthermia underlain by increased whole-body heat production. We hypothesized that elevated BAT thermogenesis plays a role in this thermoregulatory sign reversal. Using dual probe telemetric temperature implants and infrared (IR) thermography, we assessed the effects of nine repeated 60% N2O administrations compared to control (con) administrations on core temperature, BAT temperature, lumbar back temperature and tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR BAT temperature were reduced significantly during initial 60% N2O inhalation (p≤0.001 compared to con). IR thermography revealed that acute N2O administration unexpectedly reduced tail temperature (p=0.0001) and also inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation significantly increased telemetric core temperature (p=0.007) indicative of a hyperthermic sign reversal, yet compared to control administrations, telemetric BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature (p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O at 21°C may promote hypothermia via reduced BAT thermogenesis accompanied by tail vasoconstriction as a compensatory mechanism to limit body heat loss. Following repeated N2O administrations rats exhibit a hyperthermic core temperature but a normalized BAT temperature, suggesting induction of a hyperthermia-promoting thermogenic adaptation of unknown origin.

Symptoms with betel nut and betel nut with tobacco among Micronesian youth.

Betel nut has been stated to be addictive, but evidence is lacking. This study describes dependence symptoms among adolescents using betel alone or with tobacco. In the first study, participants were 151 9th graders in Saipan. In the second study, participants were 269 9th graders in Pohnpei and Yap. Participants completed a confidential questionnaire adapted from the U.S. National Survey of Drug Use and Health, which measured dependence symptoms. The 15 items were summed to form a scale, with a range of 0-15, where higher scores indicated greater endorsement of dependence symptoms. In the first study, 39.1% had used betel. More than two-thirds of all users (69.5%) used betel in the previous month: 87.8% also used tobacco with the betel. The mean (SD) dependence symptoms scale score among tobacco users was 8.2±4.0 versus 3.4±2.9 among those who used betel alone [t(7)=3.3, p=0.015]. In the second study, 38% from Pohnpei and 85% from Yap had used betel and most of the current users used it in the previous month (67% from Pohnpei, 91% from Yap). Among those who had used betel in the previous month, 90% from Pohnpei and 64% from Yap were using betel with tobacco. The dependence score was positively associated with frequency of tobacco use (e.g., mean (SD)=11.3 (±2.4) among most frequent users versus a mean (SD)=4.8 (±3.5) among the never users [F(3109)=28.8, p<0.001]). Betel nut users who also use tobacco may benefit from tobacco cessation strategies.

"Why do you want your child to have braces?" Investigating the motivations of Hispanic/Latino and white parents.

INTRODUCTION: Many psychological, social, and cultural factors influence parents' motivation to seek orthodontic care for their children. In this study, we used Q methodology to identify and categorize shared motives and determine whether cultural differences exist between Hispanic/Latino (H/L) and non-Hispanic/Latino, white (W) parents. METHODS: The fundamental question posed to the parents was "Why do you want your child to have braces?" Q methodology involves 3 stages. (1) Interviews of H/L (n = 5) and W (n = 5) parents generated 35 statements that represented different motives to seek orthodontic care. (2) In the Q sort, 70 new parents (22 H/L, 48 W) ranked statements in order of relative importance using a forced distribution grid. (3) Factor analysis was performed separately for the H/L and W groups to uncover cultural differences. RESULTS: Four motivational profiles were described for both the H/L and W parents based on the significant factors identified in each group. More H/L parents (18 of 22 parents) than W parents (22 of 48 parents) were characterized by 1 of their group's 4 profiles. Comparisons of the motivational profiles across the groups showed 4 global themes: well-timed treatment that prevents future dental problems, parental responsibility, perceived benefits, and perceived need instilled by the dentist. CONCLUSIONS: Four global themes captured the motives of most parents seeking orthodontic treatment for their children. Understanding these global themes can help clinicians frame their treatment discussions with parents.

Predicting addictive vulnerability: individual differences in initial responding to a drug's pharmacological effects.

Considerable data suggest that individuals who appear minimally disrupted during an initial drug administration have elevated risk for abusing the drug later. A better understanding of this association could lead to more effective strategies for preventing and treating drug addiction. To investigate this phenomenon using a rigorous experimental model, we first administered the abused inhalant nitrous oxide (N2O) to rats in a total calorimetry and temperature system to identify groups that were sensitive or insensitive to the drug's hypothermic effect. We then enrolled the two groups in a novel N2O self-administration paradigm. The initially insensitive rats self-administered significantly more N2O than sensitive rats, an important step in the transition to addiction. Continuous non-invasive measurement of core temperature and its underlying determinants during screening revealed that both groups had similarly increased heat loss during initial N2O administration, but that insensitive rats generated more heat and thereby remained relatively normothermic. Calorimetry testing conducted after self-administration revealed that whereas N2O's effect on heat loss persisted comparably for both groups, initially insensitive rats actually over-responded by generating excess heat and becoming hyperthermic. Thus, rats with the greatest initial heat-producing compensatory response(s) appeared initially insensitive to N2O-induced hypothermia, subsequently self-administered more N2O, and developed hyperthermic overcompensation during N2O inhalation, consistent with increased abuse potential and an allostatic model of addictive vulnerability.

Tooth wear and the role of salivary measures in general practice patients.

OBJECTIVES: The goal of this study was to investigate the association between tooth wear and salivary measures in a random sample of patients from practices of dentist members of a practice-based research network. MATERIALS AND METHODS: Patients completed a questionnaire on oral self-care, health, dietary habits, medications, and socio-demographic variables. Six salivary characteristics (consistency, resting salivary flow, resting salivary pH, stimulated salivary flow, stimulated salivary pH, and buffering capacity) were measured, and a dental examination included categorizing patients according to the dentist's judgment of the degree of tooth wear (i.e., none/minimal, some, or severe/extreme). Bivariate and multinomial logistic regression models were used to relate salivary characteristics and other factors to the outcome of tooth wear. RESULTS: Data are reported from 1,323 patients (age range 16-97 years) from 61 practices. Patient age, gender, number of teeth, and perception of dry mouth were associated with tooth wear, but salivary and dietary factors were either weakly or not related. CONCLUSIONS: The findings of this cross-sectional assessment suggest that using these salivary tests and dietary assessments in real-life clinical settings is unlikely to be useful in assessing tooth wear risk. Suggestions are offered about risk assessment for tooth wear. CLINICAL RELEVANCE: Assessing a dental patient's risk of tooth wear using salivary measures and dietary assessments as described is not recommended for general dental practice until stronger evidence exists indicating its utility.

Clarifying the roles of homeostasis and allostasis in physiological regulation.

Homeostasis, the dominant explanatory framework for physiological regulation, has undergone significant revision in recent years, with contemporary models differing significantly from the original formulation. Allostasis, an alternative view of physiological regulation, goes beyond its homeostatic roots, offering novel insights relevant to our understanding and treatment of several chronic health conditions. Despite growing enthusiasm for allostasis, the concept remains diffuse, due in part to ambiguity as to how the term is understood and used, impeding meaningful translational and clinical research on allostasis. Here, we provide a more focused understanding of homeostasis and allostasis by explaining how both play a role in physiological regulation, and a critical analysis of regulation suggests how homeostasis and allostasis can be distinguished. Rather than focusing on changes in the value of a regulated variable (e.g., body temperature, body adiposity, or reward), research investigating the activity and relationship among the multiple regulatory loops that influence the value of these regulated variables may be the key to distinguishing homeostasis and allostasis. The mechanisms underlying physiological regulation and dysregulation are likely to have important implications for health and disease.

Classification and treatment of Class II subdivision malocclusions.

INTRODUCTION: Patients with Class II subdivision malocclusions are a challenge for clinicians because reestablishing symmetry in 1 arch or both arches is often a treatment goal. In patients with mandibular skeletal asymmetry, surgery is often a treatment option. However, patients may be unwilling to undergo surgery, and other options might have to be considered. The aim of this study was to evaluate the etiologies and outcomes of Class II subdivision patients treated at the University of Washington graduate orthodontic clinic in Seattle from 1995 through 2011. METHODS: A search of patients treated between 1995 and 2011 resulted in the identification of 110 consecutively treated Class II subdivision subjects with complete records. Ninety-eight subjects could be classified into 1 of 3 groups, based on midline position and dental or skeletal etiology. Initial and final models were used to measure the peer assessment rating scores, midlines, overjet, overbite, and molar positions. Initial and final cephalograms were traced and measured. Charts were reviewed for information regarding treatment. RESULTS: Twenty-five percent of the 98 subjects had their maxillary and mandibular midlines coincident with the facial midline; their asymmetries were due to a maxillary posterior dental asymmetry. Another 15% had maxillary midlines deviated from their facial midlines, caused by maxillary anterior and posterior dental asymmetry. About 50% of the subjects had mandibular midlines that were not coincident with their facial midlines, and most of them exhibited some degree of mandibular skeletal asymmetry. Over the past 15 years, treatment strategies used at the University of Washington indicated trends toward less surgery, fewer extractions, less use of headgear, and more reliance on fixed functional appliances. Ideal correction of midlines was not always achieved, especially in patients with mandibular skeletal asymmetry, with undercorrection occurring more commonly than overcorrection. Final peer assessment rating scores were comparable, regardless of the origin of the asymmetry or the extractions status. Mandibular incisor proclination was increased when fixed functional appliances were used, as well as when a Class I molar relationship was the target for the Class II side. CONCLUSIONS: Class II subdivision malocclusions were grouped into 3 main categories; the largest category was mandibular asymmetry. Interesting trends were noted with regard to treatment strategies, midline and molar corrections, and mandibular incisor proclination.

Drug-induced regulatory overcompensation has motivational consequences: Implications for homeostatic and allostatic models of drug addiction.

Initial administration of 60% nitrous oxide (N2O) at 21°C ambient temperature (Ta) reduces core temperature (Tc) in rats, but tolerance develops to this hypothermic effect over several administrations. After additional N2O administrations, a hyperthermic overcompensation (sign-reversal) develops such that Tc exceeds control levels during N2O inhalation. This study investigated whether rats would employ behavioral thermoregulation to facilitate, or oppose, a previously acquired hyperthermic overcompensation during N2O administration. To establish a hyperthermic sign-reversal, male Long-Evans rats (N=12) received ten 3-h administrations of 60% N2O while housed in a gas-tight, live-in, "inactive" thermal gradient (~21°C). Following the tenth N2O exposure, the thermal gradient was activated (range of 10-37°C), and rats received both a control gas session and a 60% N2O test session in counterbalanced order. Mean Tc during N2O inhalation in the inactive gradient was reliably hypothermic during the first exposure but was reliably hyperthermic by the tenth exposure. When subsequently exposed to 60% N2O in the active gradient, rats selected a cooler Ta, which blunted the hyperthermic sign-reversal and lowered Tc throughout the remainder of the N2O exposure. Thus, autonomic heat production effectors mediating the hyperthermia were opposed by a behavioral effector that promoted increased heat loss via selection of a cooler ambient temperature. These data are compatible with an allostatic model of drug addiction that suggests that dysregulatory overcompensation in the drugged-state may motivate behaviors (e.g., drug taking) that oppose the overcompensation, thereby creating a vicious cycle of escalating drug consumption and recurring dysregulation.

Repeated nitrous oxide exposure in rats causes a thermoregulatory sign-reversal with concurrent activation of opposing thermoregulatory effectors.

Initial administration of 60% nitrous oxide (N2O) to rats at an ambient temperature of 21°C decreases core temperature (Tc), primarily via increased heat loss (HL). Over repeated N2O administrations, rats first develop tolerance to this hypothermia and subsequently exhibit hyperthermia (a sign-reversal) due primarily to progressive increases in heat production (HP). When rats initially receive 60% N2O in a thermal gradient, they become hypothermic while selecting cooler ambient temperatures that facilitate HL. This study investigated whether rats repeatedly administered 60% N2O in a thermal gradient would use the gradient to behaviorally facilitate, or oppose, the development of chronic tolerance and a hyperthermic sign-reversal. Male Long-Evans rats (N=16) received twelve 3-h administrations of 60% N2O in a gas-tight, live-in thermal gradient. Hypothermia (Sessions 1-3), complete chronic tolerance (Sessions 4-6), and a subsequent transient hyperthermic sign-reversal (Sessions 7-12) sequentially developed. Despite the progressive recovery and eventual hyperthermic sign-reversal of Tc, rats consistently selected cooler ambient temperatures during all N2O administrations. A final 60% N2O administration in a total calorimeter indicated that the hyperthermic sign-reversal resulted primarily from increased HP. Thus, rats did not facilitate chronic tolerance development by moving to warmer locations in the gradient, and instead selected cooler ambient temperatures while simultaneously increasing autonomic HP. The inefficient concurrent activation of opposing effectors and the development of a sign-reversal are incompatible with homeostatic models of drug-adaptation and may be better interpreted using a model of drug-induced allostasis.

Persistence of a hyperthermic sign-reversal during nitrous oxide inhalation despite cue-exposure treatment with and without a drug-onset cue.

We asked whether chronic tolerance and the hyperthermic sign-reversal induced by repeated 60% N2O exposures could be extinguished using a cue-exposure paradigm. Rats received 18 N2O administrations in a total calorimetry system that simultaneously measures core temperature (Tc), metabolic heat production (HP), and body heat loss (HL). Each exposure entailed a 2-h baseline period followed by a 1.5-h N2O exposure. The 18 drug exposures induced a robust intra-administration hyperthermia in which the initial hypothermic effect of N2O inverted to a significant hyperthermic sign-reversal during N2O inhalation due primarily to an acquired robust increase in HP. The rats were then randomized to one of three extinction procedures (n=8/procedure) over a 20-d interval: 1) a N2O-abstinent home-cage group (HC) that received only the usual animal care; 2) a cue-exposure group (CEXP) in which the animals were placed in the calorimeter 8 times but received no N2O; and 3) a drug-onset-cue group (DOC) in which animals received a brief N2O exposure in the calorimeter that mimicked the first 3 min of an actual 60% N2O trial. Following the extinction sessions, all rats received a 60% N2O test trial and Tc, HP and HL were assessed. The hyperthermic sign-reversal remained fully intact during the test trial, with no significant differences observed among groups in any post-baseline change in any thermal outcome. These data suggest that cue exposure may not be an efficacious strategy to reduce sign-reversals that develop with chronic drug use.