Calcitonin and bipolar disorder: a hypothesis revisited

Many of the great discoveries and developments in the sciences and the arts were made by people who were 'mentally different'. Some such pioneers or innovators had experiences that were indistinguishable from the phenomena defined as mental illness (or madness). It has been argued that such experiences are a necessary constituent of the creative process, and that this may apply to the sciences as much as to the arts. Increasingly, scientists propose a means by which it may be possible to identify (and eliminate) the factors that influence the altered states associated with mental illness. This may be an appropriate time to review the cultural and social significance of all forms of 'madness', especially in the light of emerging models of psychiatric nursing practice.     

Correlation of eyewitness accuracy and confidence: Optimality hypothesis revisited.

Inasmuch as a completely satisfactory estimate of effect size for the eyewitness accuracy-confidence relation does not exist, we conducted a meta-analysis of 35 staged-event studies. Estimated r?=?.25 (d?=?.52), with a 95% confidence interval of .08 to .42. Sampling error accounted for 52% of the variation in r, leaving room for measurement error and possibly moderator variables to account for the remaining variation. Further analysis identified duration of target face exposure as a moderator variable, providing support for Deffenbacher's (1980) optimality hypothesis. When corrected for the attenuating effect of sampling error in the accuracy-confidence correlations, the correlation of exposure duration and the accuracy-confidence correlation was .51: Longer exposures allowed for greater predictability of accuracy from confidence. Even through correlation for unreliability in the confidence measure produces a higher estimate of the population correlation of accuracy and confidence, .34, one must be cautious in assessing the utility of confidence for predicting accuracy in actual cases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning of and contextual sensitization to apomorphine-induced climbing in mice: Evidence against the habituation hypothesis.

Several predictions of the habituation hypothesis of conditioned drug effects were tested by looking at contextual sensitization to apomorphine-induced climbing in mice (Mus musculus). Mice were first sensitized to that effect after 9 daily injections of 0.4 mg/kg apomorphine in the test context. Other mice received the same treatment outside the test context. On Day 10, all mice were challenged with either saline (conditioned drug effects test) or apomorphine (contextual sensitization test). On both tests, the levels of climbing of mice that received apomorphine paired with the test context during the intermittent treatment were significantly higher than those of mice that were experiencing the test context for the first time (unexposed mice). Also, the rate of extinction in conditioned mice did not parallel the rate of habituation in the unexposed mice. Results contradict the habituation hypothesis of conditioned drug effects and contextual sensitization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The repulsion hypothesis revisited: Similarity irrelevance or dissimilarity bias?

Rosenbaum (1986b) proposed a reinterpretation of attraction research and theory in which similar attitudes constitute irrelevant stimuli; only dissimilar attitudes affect either attraction or performance in a learning task. He presented data seemingly consistent with these propositions, but Byrne, Clore, and Smeaton (1986) criticized the adequacy of his designs and suggested appropriate empirical tests of the competing hypotheses. This article reports two experiments in which the results are clearly inconsistent with the repulsion hypothesis. With number of dissimilar attitudes held constant, attraction toward a stranger increased as the number of similar attitudes increased. In a discrimination learning task, response acquisition occurred when correct responses were followed by similar attitude statements and incorrect responses by nonsense syllables, or when correct responses were followed by nonsense syllables and incorrect responses by dissimilar attitude statements. Despite the inadequacy of the repulsion hypothesis, Rosenbaum's analysis has raised several new and interesting possibilities for attraction research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of visual experience on the habituation of orienting behavior.

Three experiments studied the orienting behavior (OB) at 30, 60, 90, or 120 days old of male Long-Evans rats, of whom 88 were light-reared (LR) and 84 dark-reared (DR). OB was assessed by examining S's ability to interrupt ongoing licking and perform appropriate head and postural adjustments when presented with apparently moving or stationary light displays or tones. When the lights were first presented to the LR and DR Ss, their OB did not differ at any of the ages. However, age and visual experience did influence habituation and recovery of orienting with changes in the light display. The older DR Ss habituated with fewer repeated presentations of the light displays than the LR Ss and did not recover orienting as effectively to all the subsequent changes of the light displays. The younger LR and DR Ss did not differ reliably. Results are discussed with regard to the nature of the habituation process for rodents and the relation between visual experience and habituation of attentional responses. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Latent inhibition in humans: Single-cue conditioning revisited.

Latent inhibition in human Pavlovian conditioning was assessed by way of autonomic responses. In Exp 1 (N?=?72), 3 pairs of conditioning and control groups were preexposed to 0, 10, or 20 to-be-conditioned stimuli (to-be-CSs), respectively. Acquistion of electrodermal 1st-interval and heart rate response conditioning were detectable only in the zero preexposure condition. However, 20 preexposures were needed for latent inhibition of vasomotor response conditioning. In Exp 2 (N?=?48), preexposure to the to-be-CS was compared with preexposure to a stimulus that was not presented during subsequent acquisition. CS preexposure completely abolished electrodermal 1st-interval and heart rate response conditioning. Although vasomotor conditioning was not affected by preexposure, latent inhibition of 2nd-interval electrodermal response conditioning was obtained. Taken together, the data from both experiments provide clear evidence for latent inhibition in human Pavlovian conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of contextual change on latent inhibition and on the habituation of an orienting response.

In Exp I, using 20 female hooded Lister rats, the habituation of the orienting response (OR) shown by Ss to a discrete visual stimulus (a 10-sec light) in a given training context (A) was monitored. Dishabituation occurred, in that the OR returned to its initial level, when the light was presented in a different and novel context (B). In Exp II, 24 female rats received 2 sessions/day, one in each of the 2 contexts. For experimental Ss, the light was presented in Context A until the OR habituated. In the test phase, the light was presented in Context B, but the OR was not restored, suggesting that the dishabituation seen in Exp I depended on the absolute novelty of Context B. In Exp III, Ss from Exp II were required to form a light–food association in both contexts. Slow learning was observed in Ss trained with the familiar light in Context A, but learning proceeded normally with the familiar light in Context B. Thus, a context change that failed to produce dishabituation was enough to prevent the occurrence of a latent inhibition effect. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease revisited

Considering the mechanisms responsible for age- and Alzheimer's disease (AD)-related neuronal degeneration, little attention was paid to the opposing relationships between the energy-rich phosphates, mainly the availability of the adenosine triphosphate (ATP), and the activity of the glutamic acid decarboxylase (GAD), the rate-limiting enzyme synthesizing the gamma-amino butyric acid (GABA). Here, it is postulated that in all neuronal phenotypes the declining ATP-mediated negative control of GABA synthesis gradually declines and results in age- and AD-related increases of GABA synthesis. The Ca2+-independent carrier-mediated GABA release interferes with Ca2+-dependent exocytotic release of all transmitter-modulators, because the interstitial (ambient) GABA acts on axonal preterminal and terminal varicosities endowed with depolarizing GABA(A)-benzodiazepine receptors; this makes GABA the "executor" of virtually all age- and AD-related neurodegenerative processes. Such a role of GABA is diametrically opposite to that in the perinatal phase, when the carrier-mediated GABA release, acting on GABA(A)/chloride ionophore receptors, positively controls chemotactic migration of neuronal precursor cells, has trophic actions and initiates synaptogenesis, thereby enabling retrograde axonal transport of target produced factors that trigger differentiation of neuronal phenotypes. However, with advancing age, and prematurely in AD, the declining mitochondrial ATP synthesis unleashes GABA synthesis, and its carrier-mediated release blocks Ca2+-dependent exocytotic release of all transmitter-modulators, leading to dystrophy of chronically depolarized axon terminals and block of retrograde transport of target-produced trophins, causing "starvation" and death of neuronal somata. The above scenario is consistent with the following observations: 1) a 10-month daily administration to aging rats of the GABA-chloride ionophore antagonist, pentylenetetrazol, or of the BDZ antagonist, flumazenil (FL), each forestalls the age-related decline in cognitive functions and losses of hippocampal neurons; 2) the brains of aging rats, relative to young animals, and the postmortem brains of AD patients, relative to age-matched controls, show up to two-fold increases in GABA synthesis; 3) the aging humans and those showing symptoms of AD, as well as the aging nonhuman primates and rodents--all show in the forebrain dystrophic axonal varicosities, losses of transmitter vesicles, and swollen mitochondria. These markers, currently regarded as the earliest signs of aging and AD, can be reproduced in vitro cell cultures by 1 microM GABA; the development of these markers can be prevented by substituting Cl- with SO4(2-); 4) the extrasynaptic GABA suppresses the membrane Na+, K+-ATPase and ion pumping, while the resulting depolarization of soma-dendrites relieves the "protective" voltage-dependent Mg2+ control of the N-methyl-D-aspartate (NMDA) channels, thereby enabling Ca2+-dependent persistent toxic actions of the excitatory amino acids (EAA); and 5) in whole-cell patch-clamp recording from neurons of aging rats, relative to young rats, the application of 3 microM GABA, causes twofold increases in the whole-cell membrane Cl- conductances and a loss of the physiologically important neuronal ability to desensitize to repeated GABA applications. These age-related alterations in neuronal membrane functions are amplified by 150% in the presence of agonists of BDZ recognition sites located on GABA receptor. The GABA deafferentation hypothesis also accounts for the age- and AD-related degeneration in the forebrain ascending cholinergic, glutamatergic, and the ascending mesencephalic monoaminergic system, despite that the latter, to foster the distribution-utilization of locally produced trophins, evolved syncytium-like connectivities among neuronal somata, axon collaterals, and dendrites, to bidirectionally transport trophins. (ABSTRACT TRUNCATED)     

A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited

Cowan and Barron (1987) and Cowan (1989b) reported that color-naming performance was slowed by spoken color names drawn from the same set but presented in an order unrelated to the printed colors. Although Miles, Madden, and Jones (1989) and Miles and Jones (1989) were unable to replicate this cross-modal effect, it is replicated here in two experiments with much better experimental control than before. However, the effect is shown to depend upon the relative timing of the color and word in a way that conflicts with the theoretical account that Cowan and Barron offered. While Cowan and Barron suggested that an irrelevant color word would contaminate the response set if this word occupied short-term memory when the color was about to be named, it appears that interference actually occurs only if the memory representation was formed very recently and had not been inhibited. Further implications for processing are discussed.     

Overshadowing and latent inhibition counteract each other: support for the comparator hypothesis

In 4 conditioned lick suppression experiments with rats, the combined effects of latent inhibition treatment followed by overshadowing treatment were assessed as a test of the comparator hypothesis's (R.R. Miller & L.D. Matzel, 1988) explanations of overshadowing and latent inhibition. Experiments 1 and 2 confirmed the prediction of the comparator hypothesis that combined latent inhibition and overshadowing treatments attenuate the response deficit produced by either treatment alone. Furthermore, consistent with the comparator hypothesis, posttraining changes in the associative status of the putative comparator stimulus altered responding to the target conditioned stimulus (Experiment 3), and switching contexts between latent inhibition and overshadowing treatments (Experiment 4) eliminated the interaction between the latent inhibition and overshadowing treatments.     

Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia

1. The authors have recently proposed that the sensitization produced by repeated exposure to drugs or stress may give way to an alternating pattern of increases and decreases in the response to each subsequent exposure (i.e., oscillate), as the limits of the physiological system are approached. 2. Evidence for oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical or endocrine endpoints. This paper extends the model to a behavioral outcome. 3. In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal latencies from a hot-plate. 4. The second experiment replicated the first and extended the pretreatment sequence to 5 COC injections. 5. In both experiments, shock significantly increased latencies over the no-shock controls. COC enhanced shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC pretreatments. Thereafter, oscillation developed such that the sensitization was attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and reattenuated after 5 COC pretreatments. 6. These data complement other findings by demonstrating that the oscillation model extends to a stress-induced behavioral outcome.     

Effect of naloxone on conditioned suppression in rats.

Painful stimuli are known to engage an endorphin analgesic system that can be reversed by the opiate antagonist, naloxone. Naloxone, then, should increase the effectiveness of aversive unconditioned stimulus/stimuli (UCS) in Pavlovian fear conditioning. Consistent with this hypothesis, naloxone administered during the acquisition of conditioned suppression in rats enhanced posttrial suppression and preconditioned stimulus (pre-CS; context-controlled) suppression. Furthermore, it enhanced CS-elicited suppression during extinction when administered during acquisition but not when administered only during extinction. Thus naloxone does not enhance an already existing fear nor enhance the memory of previous conditioning; instead, it enhances the conditioning of fear presumably by making the aversive UCS more painful. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of platelet activation on coronary collateral blood flow

BACKGROUND: The platelet products thromboxane A2 and serotonin have been shown to cause constriction of well-developed coronary collateral vessels. This study was performed to determine whether intravascular platelet activation produced with platelet activating factor (PAF) can cause a decrease in coronary collateral blood flow. METHODS and RESULTS: Collateral vessel growth was induced by embolization of a hollow stainless steel plug into the left anterior descending coronary artery (LAD) of adult dogs. The animals were returned to the laboratory 3 to 6 weeks later for surgical instrumentation and measurement of collateral blood flow. Collateral flow was assessed by measuring retrograde blood flow from the cannulated collateral-dependent artery. PAF (10 nmol) was injected into the left main coronary artery to allow products of platelet activation to reach collateral vessels arising from the left coronary system. PAF caused a vasoconstrictor response, which became maximal 3 minutes after injection and resulted in a 40.3+/-7.4% decrease in retrograde blood flow (32.1+/-2.1 to 19.6+/-3.2 mL/min; P<0.05). By 15 minutes after the PAF injection, both retrograde blood flow and transcollateral resistance had returned to normal. After pretreatment with the thromboxane A2 receptor antagonist SQ30, 741, the vasoconstrictor response to PAF was abolished and, in contrast to the decrease in retrograde blood flow from PAF alone, a weak vasodilator effect was unmasked. CONCLUSIONS: PAF caused a decrease in coronary collateral blood flow. This vasoconstrictor response required the participation of thromboxane A2.     

Determinants of the nature of environmentally induced hypoalgesia.

Factors that determine whether naltrexone and pentobarbital anesthesia block the hypoalgesia produced by electric shock were investigated. One shock was followed by an initial hypoalgesia that was reversed by naltrexone but was not affected by pentobarbital. When testing was conducted in the shock context, early hypoalgesia was followed by a hypoalgesia that was still reversed by naltrexone but was eliminated by pentobarbital anesthesia. This second hypoalgesia did not occur when testing was conducted after removing the animal from the shock apparatus. Five shocks were also followed by 2 separable responses. The first response was not reduced by pentobarbital, but it was not blocked by naltrexone. This initial response was not prevented by removal from the shock context, but the 2nd response did not occur after removal. The pattern after 80 shocks was quite different. Here the hypoalgesic response did not appear to change in character across the 10 min of testing or with removal from the shock apparatus. The response persisted for 10 min in the shock context or after removal and was blocked by both naltrexone and pentobarbital throughout its entire duration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.     

Effect of naloxone on the bladder activity of rabbits with acute spinal injury

BACKGROUND: Naloxone enhances bladder activity in patients with chronic spinal cord injury. However, there are few reports on naloxone for bladder morbidity in acute spinal cord injury. METHODS: We performed a prospective, controlled study of the effects of naloxone on bladder function in rabbits with and without surgical transection of the spinal cord at the 10th thoracic vertebra. Acute and chronic stages of injury were defined according to bladder function. Naloxone was given intravenously at both stages, and intrathecally at the acute stage. Bladder activity was monitored by cystometry. Blood concentrations of methionine-enkephalin were measured by radioimmunoassay. RESULTS: Spinal cord injuries were acute 1 or 2 days after surgery, and chronic after 1 or 2 weeks. Bladder capacity significantly decreased after 0.01 mg of intravenous naloxone in uninjured control rabbits, and after 0.03 mg of intravenous naloxone in rabbits with chronic-phase injuries. During the acute-injury phase, 0.3 mg of intravenous naloxone, or 0.02 mg of intrathecal naloxone, was necessary to evoke the micturition reflex. No significant changes in blood enkephalin levels were seen before or after spinal cord injury. CONCLUSION: In rabbits with acute spinal cord injury, intrathecal naloxone evoked the micturition reflex at a much lower dose than did intravenous naloxone. Intrathecal naloxone promises to become a new therapy for the acute stage of spinal cord injury for active recovery of bladder function, and could replace current therapy.