Latent Sensitization Research Articles

Assessing learned associations between conditioned cocaine reward and environmental stimuli in the Wistar Kyoto rat

Clinical studies demonstrate that anxiety disorders increase the risk of substance use disorder. However, few studies have directly assessed anxiety as a vulnerability factor in processing of rewarding stimuli. The Wistar–Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability because it exhibits extreme behavioral inhibition in novel and social environments; yet, it displays paradoxical rapid active avoidance learning that is resistant to extinction. The present study was designed to characterize the acquisition and persistence of cocaine conditioned place preference (CPP) in WKY rats. In the first of a series of three experiments, adult male WKY and Sprague Dawley (SD) rats were given six pairings of cocaine (3, 5, 10, 15mg/kg) or saline on alternating days. SD rats developed cocaine-induced CPP to each of the four doses of cocaine tested. In contrast, WKY rats demonstrated CPP when conditioned with 3, 5, and 10mg/kg, but displayed no preference to the 15mg/kg dose. Next, separate groups of rats were subject to an extended CPP paradigm, which included acquisition, extinction and reinstatement phases. Rats were conditioned with cocaine and saline on alternating days using either a 6/6 (as above) or 4/4 conditioning regimen. Both SD and WKY rats acquired a lasting CPP with the 6/6 conditioning regimen. Results from the 4/4 conditioning regimen show that SD, but not WKY, rats acquired CPP. Preference scores for SD rats during the cocaine primed reinstatement test were significantly different from pretest scores indicating reinstatement of CPP in this group. Paradoxically, WKY rats demonstrated a latent sensitization to the conditioned rewarding effects of cocaine during the drug-primed reinstatement test. Taken together, WKY rats appear to be more sensitive to high doses of cocaine and need more experience with the drug to acquire a preference than SD rats.

On the discrepant results in synchrony judgment and temporal-order judgment tasks: a quantitative model

Research on the perception of temporal order uses either temporal-order judgment (TOJ) tasks or synchrony judgment (SJ) tasks, in both of which two stimuli are presented with some temporal delay and observers must judge the order of presentation. Results generally differ across tasks, raising concerns about whether they measure the same processes. We present a model including sensory and decisional parameters that places these tasks in a common framework that allows studying their implications on observed performance. TOJ tasks imply specific decisional components that explain the discrepancy of results obtained with TOJ and SJ tasks. The model is also tested against published data on audiovisual temporal-order judgments, and the fit is satisfactory, although model parameters are more accurately estimated with SJ tasks. Measures of latent point of subjective simultaneity and latent sensitivity are defined that are invariant across tasks by isolating the sensory parameters governing observed performance, whereas decisional parameters vary across tasks and account for observed differences across them. Our analyses concur with other evidence advising against the use of TOJ tasks in research on perception of temporal order.

A 18F-fluorodeoxyglucose MicroPET Imaging Study to Assess Changes in Brain Glucose Metabolism in a Rat Model of Surgery-induced Latent Pain Sensitization

Neuroplastic changes involved in latent pain sensitization after surgery are poorly defined. We assessed temporal changes in glucose brain metabolism in a postoperative rat model using positron emission tomography. We also investigated brain metabolism after naloxone administration. Rats were given remifentanil anesthetic and underwent a plantar incision, with 1 mg/kg of (-)-naloxone subcutaneously administered on postoperative days 20 and 21. Using the von Frey test, mechanical thresholds were measured pre- and postoperatively at different time points in awake animals during F-fluorodeoxyglucose (F-FDG) uptake. Brain images were also obtained the day before mechanical testing, using a positron emission tomography R4 scanner (Concorde Microsystems, Siemens, Knoxville, TN). Differences in brain activity were assessed utilizing a statistical parametric mapping. Surgery induced minor changes in F-FDG uptake in the cerebellum, hippocampus, and posterior cortex, which extended to the thalamus, hypothalamus, and brainstem on days 6 and 7. Changes were still present on day 21. Maximal postoperative hypersensitivity was observed on day 2. The administration of (-)-naloxone on day 21 induced significant hypersensitivity, greatly enhancing the effect on F-FDG uptake. In sham-operated rats, naloxone induced changes limited to the striatum and the cerebellum. Nonnociceptive stimulation with von Frey filaments had no effect on F-FDG uptake. Surgery, remifentanil, and their combination induced long-lasting and significant metabolic changes in the pain brain matrix, with a positive correlation with hypersensitivity after naloxone. Changes in brain F-FDG precipitated by naloxone suggest that surgery under remifentanil anesthetic induces the greatest neuroplastic brain adaptations in opioid-related pathways involved in nociceptive processing and long-lasting pain sensitization.

Effects of Burst-Type Transcutaneous Electrical Nerve Stimulation on Cervical Range of Motion and Latent Myofascial Trigger Point Pain Sensitivity

Rodríguez-Fernández AL, Garrido-Santofimia V, Güeita-Rodríguez J, Fernández-de-las-Peñas C. Effects of burst-type transcutaneous electrical nerve stimulation on cervical range of motion and latent myofascial trigger point pain sensitivity. Objective To assess the effects of a burst application of transcutaneous electrical nerve stimulation (TENS) on cervical range of motion and pressure point sensitivity of latent myofascial trigger points (MTrPs). Design A single-session, single-blind randomized trial. Setting General community rehabilitation clinic. Participants Individuals (N=76; 45 men, 31 women) aged 18 to 41 years (mean ± SD, 23±4y) with latent MTrPs in 1 upper trapezius muscle. Interventions Subjects were randomly divided into 2 groups: a TENS group that received a burst-type TENS (pulse width, 200μs; frequency, 100Hz; burst frequency, 2Hz) stimulation over the upper trapezius for 10 minutes, and a placebo group that received a sham-TENS application over the upper trapezius also for 10 minutes. Main Outcome Measures Referred pressure pain threshold (RPPT) over the MTrP and cervical range of motion in rotation were assessed before, and 1 and 5 minutes after the intervention by an assessor blinded to subjects' treatment. Results The analysis of covariance revealed a significant group × time interaction ( P<.001) for RPPT: the TENS group exhibited a greater increase compared with the control group; however, between-group differences were small at 1 minute (0.3kg/cm 2; 95% confidence interval [CI], 0.1–0.4) and at 5 minutes (0.6kg/cm 2; 95% CI, 0.3–0.8) after treatment. A significant group × time interaction ( P=.01) was also found for cervical rotation in favor of the TENS group. Between-group differences were also small at 1 minute (2.0°; 95% CI, 1.0–2.8) and at 5 minutes (2.7°; 95% CI, 1.7–3.8) after treatment. Conclusions A 10-minute application of burst-type TENS increases in a small but statistically significant manner the RPPT over upper trapezius latent MTrPs and the ipsilateral cervical range of motion.

Endogenous Opioids Released During Non-Nociceptive Environmental Stress Induce Latent Pain Sensitization Via a NMDA-Dependent Process

Although stress induces analgesia, there is evidence that stressful events may exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful events (days 0, 2, and 7), such as non-nociceptive environmental stress, on inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat hind paw. Changes in nociceptive threshold were evaluated by the paw pressure vocalization test. The higher the number of stress sessions presented to the rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors by naltrexone before each stress inhibited stress-induced analgesia and suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed animals could be discriminated by their response to a fentanyl ultra-low dose (fULD), that produced hyperalgesia or analgesia, respectively. This pharmacological test permitted the prediction of the pain vulnerability level of prestressed rats because fULD analgesic or hyperalgesic indices were positively correlated with inflammatory hyperalgesic indices (r 2 = .84). In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists. This study provides some preclinical evidence that pain intensity is not only the result of nociceptive input level but is also dependent on the individual history, especially prior life stress events associated with endogenous opioid release. Perspective Based on these preclinical data, it would be of clinical interest to evaluate whether prior stressful events may also affect further pain sensation in humans. Moreover, this preclinical model could be a good tool for evaluating new therapeutic strategies for relieving pain hypersensitivity.

Latent nociceptive sensitization requires the maintenance mechanism of LTP

Latent nociceptive sensitization requires the maintenance mechanism of LTP

Delayed postoperative latent pain sensitization revealed by the systemic administration of opioid antagonists in mice

The long-lasting post-surgical changes in nociceptive thresholds in mice, indicative of latent pain sensitization, were studied. The contribution of kappa opioid and N-methyl- d-aspartate (NMDA) receptors was assessed by the administration of nor-binaltorphimine or MK-801; dynorphin levels in the spinal cord were also determined. Animals underwent a plantar incision and/or a subcutaneous infusion of remifentanil (80 μg/kg), and mechanical thresholds (von Frey) were evaluated at different times. On day 21, after complete recovery of mechanical thresholds and healing of the wound, one of the following drugs was administered subcutaneously: (−)-naloxone (1 mg/kg), (+)-naloxone (1 mg/kg), naloxone-methiodide (3 mg/kg), or nor-binaltorphimine (5 mg/kg). Another group received subcutaneous MK-801 (0.15 mg/kg) before nor-binaltorphimine administration. Dynorphin on day 21 was determined in the spinal cord by immunoassay. In mice receiving remifentanil during surgery, the administration of (−)-naloxone or nor-binaltorphimine induced significant hyperalgesia even 5 months after manipulation. Nociceptive thresholds remained unaltered after (+)-naloxone or naloxone-methiodide. On day 21 after manipulation, the administration of MK-801 prevented nor-binaltorphimine-induced hyperalgesia. No changes in dynorphin levels were observed before or after opioid antagonist administration. In conclusion, surgery produced latent pain sensitization evidenced by opioid antagonist-precipitated hyperalgesia. The effect was stereospecific, centrally originated, and mediated by kappa opioid receptors. The blockade of nor-binaltorphimine-induced hyperalgesia by MK-801, suggests that NMDA receptors are also involved. Our results show for the first time that surgery induces latent, long-lasting changes in the processing of nociceptive information that can be induced by non-nociceptive stimuli such as the administration of opioid antagonists.

Dizziness and the genetic influences on subjective experiences to initial cigarette use

To examine individual differences in positive and negative subjective experiences to initial cigarette use. Retrospective self-reports of initial subjective experiences were examined to estimate the genetic and environmental influences and the extent of their covariation across different effects. Data was drawn from 2482 young adult same-and opposite sex twins- and siblings participating in the National Longitudinal Study of Adolescent Health. Subjective experiences were retrospectively collected using the Early Smoking Experience (ESE) questionnaire. Positive experiences evidenced moderate heritable contributions (40%, 95% CI: 0.22 to 0.56), as did an overall hedonic measure (34%, 95% CI: 0.22 to 0.46) and dizziness (34%, 95% CI: 0.15 to 0.52). Negative experiences evidenced small heritable contributions (13%, 95% CI: 0.00 to 0.36). Individual specific environmental influences were strong and accounted for the remaining proportion of observed variation in these experiences. Multivariate genetic modeling identified a moderately heritable underlying factor (37%, 95% CI: 0.22 to 0.52) that influenced the covariation of diverse subjective experiences and loaded most heavily on dizziness. Positive experiences also evidence residual genetic influences that were uncorrelated with other subjective experiences. How a person experiences their initial few cigarettes is due to both heritable contributions and environmental experiences unique to the person. The covariation of diverse subjective experiences appears to be due to a heritable latent sensitivity to the chemicals contained in an average cigarette and is best indexed by dizziness.

Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity

Exposure to opioids can induce a state of “latent sensitization” characterized by long-lasting enhanced responses to subsequent cutaneous injury. Here, we explored the possibility that prior treatment with morphine could induce a state of latent sensitization to visceral pain conditions. Following butyrate enemas to induce non-inflammatory visceral pain, acute morphine administration produced dose-related inhibition of referred viscerosomatic hypersensitivity. Treatment with morphine for a period of six days resulted in a persistent hyperalgesia that resolved many days after termination of drug administration. In morphine pre-exposed rats, butyrate-induced referred hypersensitivity was enhanced and extended in duration. No differences were observed in the morphine dose–response curve in suppression of acute nociception (i.e., the hot-plate assay) when morphine pre-exposed rats were compared to naïve rats indicating that opioid antinociceptive tolerance was not present. However, the morphine dose–response curve to suppress evoked viscerosomatic hypersensitivity was displaced to the right by approximately 4-fold in morphine pre-exposed rats. Induction of viscerosomatic hypersensitivity resulted in an increased labeling of CGRP-, but not substance P-positive cells in the lumbar dorsal root ganglia; increased labeling was not affected by prior exposure to morphine. The data indicate that a period of morphine exposure can induce a state of “latent sensitization” to subsequent visceral pain characterized by extended duration of hypersensitivity. This condition likely reflects enhanced visceral “pain” intensity as a consequence of persistent pronociceptive adaptive changes.

Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers

Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene related peptide. Additionally, triptan administration elicited a behavioural syndrome of enhanced sensitivity to surrogate triggers of migraine that was maintained for weeks following discontinuation of drug, a phenomenon termed 'triptan-induced latent sensitization'. Here, we demonstrate that triptan administration elicits a long-lasting increase in identified rat trigeminal dural afferents labelled for neuronal nitric oxide synthase in the trigeminal ganglion. Cutaneous allodynia observed during the period of triptan administration was reversed by NXN-323, a selective inhibitor of neuronal nitric oxide synthase. Additionally, neuronal nitric oxide synthase inhibition prevented environmental stress-induced hypersensitivity in the post-triptan administration period. Co-administration of NXN-323 with sumatriptan over several days prevented the expression of allodynia and enhanced sensitivity to stress observed following latent sensitization, but not the triptan-induced increased labelling of neuronal nitric oxide synthase in dural afferents. Triptan administration thus promotes increased expression of neuronal nitric oxide synthase in dural afferents, which is critical for enhanced sensitivity to environmental stress. These data provide a biological basis for increased frequency of headache following triptans and highlight the potential clinical utility of neuronal nitric oxide synthase inhibition in preventing or treating medication overuse headache.

An analysis of consumption behaviour of foreign tourists in Ireland

The objective of this article is to analyse the consumption behaviour of foreign tourists in Ireland. Based on the Almost Ideal Demand System, five demand systems are estimated, four representing the major source markets of tourists to Ireland, namely from Britain, North America, Mainland Europe and Rest of the World; and one aggregate model based on a pooled sample. Each system included six commodity aggregates representing the major consumables of tourists. Estimated models were statistically significant and the derived elasticities are theoretically consistent and empirically plausible. While there are some variations in the consumption patterns of tourists from different source markets, reflecting differences in consumer preferences and consumption habits, in general, tourist demand for the various Irish tourism goods and services is found to be price inelastic. This finding is consistent with a priori expectations, as tourists are obliged to consume whatever is available at the destination they visit. The lack of substitutes and perfect information on product markets offer limited consumption opportunities for the tourists. Nonetheless, the cross-price elasticity values for all commodities across the source markets indicate gross complementarity, which suggests that latent price sensitivity exists in the background. This is an area that needs further investigation and this finding may have significant, yet unknown, consequences for repeat visitation.

Triptan‐induced latent sensitization: A possible basis for medication overuse headache

Identification of the neural mechanisms underlying medication overuse headache resulting from triptans. Triptans were administered systemically to rats by repeated intermittent injections or by continuous infusion over 6 days. Periorbital and hind paw sensory thresholds were measured to detect cutaneous allodynia. Immunofluorescent histochemistry was employed to detect changes in peptidic neurotransmitter expression in identified dural afferents. Enzyme-linked immunoabsorbent assay was used to measure calcitonin gene-related peptide (CGRP) levels in blood. Sustained or repeated administration of triptans to rats elicited time-dependent and reversible cutaneous tactile allodynia that was maintained throughout and transiently after drug delivery. Triptan administration increased labeling for CGRP in identified trigeminal dural afferents that persisted long after discontinuation of triptan exposure. Two weeks after triptan exposure, when sensory thresholds returned to baseline levels, rats showed enhanced cutaneous allodynia and increased CGRP in the blood following challenge with a nitric oxide donor. Triptan treatment thus induces a state of latent sensitization characterized by persistent pronociceptive neural adaptations in dural afferents and enhanced responses to an established trigger of migraine headache in humans. Triptans represent the treatment of choice for moderate and severe migraine headaches. However, triptan overuse can lead to an increased frequency of migraine headache. Overuse of these medications could induce neural adaptations that result in a state of latent sensitization, which might increase sensitivity to migraine triggers. The latent sensitization could provide a mechanistic basis for the transformation of migraine to medication overuse headache.

Economics of Leisure and Non-Leisure Tourist Demand: A Study of Domestic Demand for Australian Tourism

This article analyses the economic determinants of demand for tourism goods and services by Australian households distinguished by the travel motives of leisure and non-leisure. Using tourist consumption data collected through quarterly national visitor surveys, two systems of demand equations are estimated, based on the almost ideal demand system and incorporating seasonality. The study aggregates itemized tourist expenditure data into five broad commodity groups: accommodation, food, transportation, shopping and entertainment. The estimated models obey the basic postulates of consumer theory – homogeneity and symmetry. Overall, demand for the five commodity aggregates is found to be price inelastic, while the degree of price sensitivity varies across the commodity aggregates and between the two types of tourists. In general, demand by leisure tourists is found to be more sensitive to price than demand by non-leisure tourists. The cross-price elasticities derived from both models reveal a gross complementarity of demand, implying that tourists' overall utility depends on the joint consumption of a bundle of goods and services. The observed price-inelastic demand, coupled with the apparent complementarity of demand, may reflect the possibility that latent price sensitivity is associated with tourist demand.

Chronic ∆ 9-tetrahydrocannabinol during adolescence increases sensitivity to subsequent cannabinoid effects in delayed nonmatch-to-position in rats

Early-onset marijuana use has been associated with short- and long-term deficits in cognitive processing. In human users, self-selection bias prevents determination of the extent to which these effects result only from drug use. This study examined the long-term effects of Δ 9-tetrahydrocannabinol (Δ 9-THC), the major psychoactive constituent of marijuana, in a delayed nonmatch-to-position task (DNMP). Male Long–Evans rats were injected daily with 10 mg/kg Δ 9-THC during or after adolescence [postnatal days (PN) 21–50 or PN50–79, respectively] or with vehicle. On PN91, training in DNMP was initiated. Successful acquisition and pharmacological challenge began on approximately PN300. Decreases in accuracy were observed at lower doses of Δ 9-THC in Δ 9-THC-treated rats (versus vehicle-treated rats). Administration of chronic Δ 9-THC at a younger age tended to enhance this effect. While anandamide did not decrease accuracy in any group, rats treated with Δ 9-THC during adolescence initiated fewer trials at the 30 mg/kg dose of anandamide than did rats in the other two groups. To the extent tested, these differences were pharmacologically selective for cannabinoids, as scopolamine (positive control) decreased accuracy at the same dose in all groups and amphetamine (negative control) did not affect accuracy in any of the groups at doses that did not impair overall responding. These results suggest that repeated administration of a modest dose of Δ 9-THC during adolescence (PN21–50) or shortly thereafter (PN50–79) produces a long-term increase in latent sensitivity to cannabinoid-induced impairment of performance in a complex operant task.

Economics of Domestic Tourism: A Study of Australian Demand for Tourism Goods and Services

This study analyzes the economic determinants of domestic demand for tourism goods and services by Australians in a preference-consistent utility maximization framework. A system of demand equations based on the almost ideal demand system, which incorporates seasonality, is estimated using tourist consumption data collected through quarterly national visitor surveys. The system consists of five commodity aggregates: accommodation, food, transportation, shopping, and entertainment. The estimated model obeys the basic postulates of consumer theory, homogeneity, and symmetry. The results indicate that demands are price inelastic while income elasticities varied significantly in magnitude across the commodity aggregates. It was also observed that the demands for the five commodity aggregates are complementary, implying that tourists' overall utility depends on the joint consumption of a bundle of goods and services. The observed price inelastic demand coupled with the apparent complementarity of demands across the consumption bundle may be reflective of the possibility that latent price sensitivity is associated with tourist demand.

Prevalence estimation and validation of new instruments in psychiatric research: An application of latent class analysis and sensitivity analysis.

Prevalence and validation studies rely on imperfect reference standard (RS) diagnostic instruments that can bias prevalence and test characteristic estimates. The authors illustrate 2 methods to account for RS misclassification. Latent class analysis (LCA) combines information from multiple imperfect measures of an unmeasurable latent condition to estimate sensitivity (Se) and specificity (Sp) of each measure. With simple algebraic sensitivity analysis (SA), one uses researcher-specified RS misclassification rates to correct prevalence and test characteristic estimates and can succinctly summarize a range of scenarios with Monte Carlo simulation. The authors applied LCA to a validation study of a new substance use disorder (SUD) screener and a larger prevalence study. With a traditional validation study analysis in which an error-free RS (Structured Clinical Interview for DSM-IV Axis I Disorders [SCID]; M. H. First, R. L. Spitzer, M. Gibbon, & J. Williams, 1990) is assumed, the authors estimated the screener had 86% Se and 75% Sp. Validation study estimates from LCA were 91% Se, 81% Sp (screener), 73% Se, and 98% Sp (SCID). SA in the prevalence study suggested the prevalence of SUD was underestimated by 22% because SCID was assumed to be error-free. LCA and SA can assist investigators in relaxing the unrealistic assumption of perfect RSs in reporting prevalence and validation study results.

Prevalence estimation and validation of new instruments in psychiatric research: An application of latent class analysis and sensitivity analysis.

Prevalence estimation and validation of new instruments in psychiatric research: An application of latent class analysis and sensitivity analysis.

Triagem neonatal para infecção chagásica congênita: aplicação de análise de classe latente para avaliação dos testes diagnósticos

The present study had the aim of evaluating conventional serum tests that are used in neonatal screening for Chagas disease, with a discussion on the statistical methods available. A random sample among 23,308 newborns who were screened for congenital Chagas disease was studied using the following three tests: enzyme immunoassay, indirect immunofluorescence and indirect hemagglutination. The data were analyzed by different statistical methodologies: latent class analysis, Kappa test and relative sensitivity analysis. Using latent class analysis, enzyme immunoassay had the highest sensitivity (48.6%), followed by indirect immunofluorescence (39.8%) and indirect hemagglutination (23.2%). The kappa value was 0.496. The ratio between the sensitivities of enzyme immunoassays and indirect immunofluorescence tests was 92% [0.74;1.13]. Latent class analysis was not found to be adequate for sensitivity and specificity determination, but it provided important data about the equivalence of the tests, corroborated by relative sensitivity analysis. The results showed that enzyme immunoassaying of dry blood samples can be used as safely as the indirect immunofluorescence test.

Changes in apical dendritic structure correlate with sustained ERK1/2 phosphorylation in medial prefrontal cortex of a rat model of dopamine D1 receptor agonist sensitization.

Rats lesioned with 6-hydroxydopamine (6-OHDA) as neonates exhibit behavioral and neurochemical abnormalities in adulthood that mimic Lesch-Nyhan disease, schizophrenia, and other developmental disorders of frontostriatal circuit dysfunction. In these animals a latent sensitivity to D1 agonists is maximally exposed by repeated administration of dopamine agonists in the postpubertal period (D1 priming). In neonate-lesioned, adult rats primed with SKF-38393, we found selective, persistent alterations in the morphology of pyramidal neuron apical dendrites in the prelimbic area of the medial prefrontal cortex (mPFC). In these animals, dendrite bundling patterns and the typically straight trajectories of primary dendritic shafts were disrupted, whereas the diameter of higher-order oblique branches was increased. Although not present in neonate-lesioned rats treated with saline, these morphological changes persisted at least 21 days after repeated dosing with SKF-38393, and were not accompanied by markers of neurodegenerative change. A sustained increase in phospho-ERK immunoreactivity in wavy dendritic shafts over the same period suggested a relationship between prolonged ERK phosphorylation and dendritic remodeling in D1-primed rats. In support of this hypothesis, pretreatment with the MEK1/2-ERK1/2 pathway inhibitors PD98059 or SL327, prior to each priming dose of SKF-38393, prevented the morphological changes associated with D1 priming. Together, these findings demonstrate that repeated stimulation of D1 receptors in adulthood interacts with the developmental loss of dopamine to profoundly and persistently modify neuronal signaling and dendrite morphology in the mature prefrontal cortex. Furthermore, sustained elevation of ERK activity in mPFC pyramidal neurons may play a role in guiding these morphological changes in vivo.

Measurement invariance versus selection invariance: Is fair selection possible?

This article shows that measurement invariance (defined in terms of an invariant measurement model in different groups) is generally inconsistent with selection invariance (defined in terms of equal sensitivity and specificity across groups). In particular, when a unidimensional measurement instrument is used and group differences are present in the location but not in the variance of the latent distribution, sensitivity and positive predictive value will be higher in the group at the higher end of the latent dimension, whereas specificity and negative predictive value will be higher in the group at the lower end of the latent dimension. When latent variances are unequal, the differences in these quantities depend on the size of group differences in variances relative to the size of group differences in means. The effect originates as a special case of Simpson's paradox, which arises because the observed score distribution is collapsed into an accept-reject dichotomy. Simulations show the effect can be substantial in realistic situations. It is suggested that the effect may be partly responsible for overprediction in minority groups as typically found in empirical studies on differential academic performance. A methodological solution to the problem is suggested, and social policy implications are discussed.