Supplementation with Phaseolus vulgaris Leaves Improves Metabolic Alterations Induced by High-Fat/Fructose Diet in Rats Under Time-Restricted Feeding.

Time-restricted feeding and food enriched in polyphenols are strategies to prevent or reduce metabolic disorders. Bean leaves (Phaseolus vulgaris L.) are a recognized source of polyphenolic compounds, whose effects on metabolic pathways are not well studied. We evaluated the combined effects of dietary supplementation with Phaseolus vulgaris leaves (10% w/w) (BL) and a 7-h daytime-restricted feeding protocol (RF) under a hypercaloric diet (high fat + high fructose) (HFFD) on the metabolic parameters related to glucose and lipid handling. Adult male Wistar rats were treated for 8 weeks with standard and HFFD diets with or without BL. The results showed that RF improved metabolic alterations induced by HFFD (e.g., hepatic steatosis, increased triacylglycerols, and serum lipoproteins). Supplementation with BL significantly enhanced this effect and downregulated the mRNA expression of carbohydrate and lipid metabolism genes in the liver. These results indicate that dietary supplementation with BL enhances the benefits elicited by RF.

Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

Two key proteins for cellular communication between astrocytes and neurons are αvß3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvß3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvß3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the ß3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvß3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication.

Genes coding for transporters showed a rapid and sharp increase in their expression in response to lead, in the aquatic fern (Salvinia minima Baker).

Salvinia minima was assessed for its ability to accumulate lead (Pb) by exposing it to concentrations of 40µM Pb(NO3)2 during 24h. At the same time, the expression levels were quantified, of four genes coding for transporters: SmABCC (ABCC-MRP), SmATPase (ATPase-P3A), SmNhaD (Type-Na+/H+) and SmABCG (ABCG-WBC). In the absence of lead, S. minima had very low expression of those genes, when plants were exposed to the metal however, those genes showed a rapid (in just three hours or less) and sharp increase (up to 60 times) in their expression, particularly the SmNhaD (Type-Na+/H+) gene. This sharp increase in expression levels of the genes studied, occurred at the same time that the plant accumulated the highest content of lead in its tissues. The first two genes, are apparently implicated in detoxification and lead accumulation mechanisms, while the other two genes are apparently involved in maintaining cell balance (homeostatic control) and membrane integrity. Our results confirmed that S. minima is efficient for phytoremediation of water bodies contaminated by lead, as it is efficient in accumulating this metal in its tissues (bioconcentration factor; BCF) values greater than 1000, in short times of exposure. More importantly, our data on the expression profiles of four genes coding for transporters, represent a first sight scenario of the molecular basis for understanding the different mechanism of detoxification, apparently present in this aquatic fern.

Latitudinal prevalence gradient of multiple sclerosis in Latin America.

BACKGROUND: Multiple sclerosis (MS) has a unique geographical distribution that reflects both genetic and environmental factors. Many studies have shown a positive correlation between MS frequency and latitude across both large and small geographical regions. However, scarce data have been published on the epidemiology of MS in Latin America and no study has evaluated latitudinal variation. OBJECTIVE: To evaluate the effect of latitude on MS prevalence in Latin America. METHODS: We conducted a systematic review of MS prevalence during January 2011. Prevalence rates were collected from eligible publications. The effect of latitude on prevalence was analyzed using linear regression. RESULTS: A total of ten studies were eligible for analysis, corresponding to six countries, spanning from Panama to Argentina. The crude prevalence of MS ranged from 0.75 to 21.5 per 100,000. We found a strong and significant association between prevalence and latitude (r(2) 0.8; p < 0.001) and determined an increase in prevalence of 0.33 per 100,000 per degree latitude. CONCLUSION: Our findings suggest a latitudinal prevalence gradient of MS in Latin American countries between Panama and Argentina.

Memory consolidation and reconsolidation in an invertebrate model: the role of the GABAergic system.

Consolidation theory assumes that memories are labile during a limited time window after acquisition, but as time passes, memories become stable and resistant to amnesic agents. However, the vision of immutable memories after consolidation has been challenged. Thus, after the presentation of a reminder, the reactivated old memories become labile and again susceptible to amnesic treatments. This process implies a re-stabilization phase, usually referred to as reconsolidation. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter both in the Central nervous system (CNS) and in the periphery. A considerable amount of evidence has arisen from different studies regarding the role of the GABA(A) receptor in diverse behavioral paradigms and tasks. Here, we investigate the role of the GABAergic system on both memory consolidation and reconsolidation phases by using the memory paradigm of the crab Chasmagnathus. In order to achieve such a goal, we design pharmacological-behavioral experiments, which include the administration of classic agonist (muscimol) and antagonist (bicuculline) of the mammals GABA(A) receptors. The current results show that the systemic administration of muscimol impairs the consolidation and reconsolidation processes. In contrast, the administration of bicuculline improves the consolidation and reconsolidation processes. Furthermore, the co-administration of both drugs blocks the agonist amnesic effect on the consolidation phase. The ubiquity of the neurotransmitter and its receptors in the animal taxa allows us to use the classic agonist-and-antagonist administration procedure in this invertebrate. Thus, all the results reported in this paper can be judged as a result of the modulation exerted by the functional state of the GABAergic system in the CNS. To conclude, the results obtained in this report with an invertebrate model represent additional evidences supporting the view that some molecular mechanisms subserving different memory phases could be the basic tools employed by phylogenetically disparate animals.

Human reconsolidation does not always occur when a memory is retrieved: the relevance of the reminder structure.

Memory reconsolidation is defined as a process in which the retrieval of a previously consolidated memory returns to a labile state which is then subject to stabilization. The reminder is the event that begins with the presentation of the learned cue and triggers the labilization-reconsolidation process. Since the early formulation of the hypothesis, several controversial items have arisen concerning the conditions that define reconsolidation. It is herein proposed that two diagnostic features characterize reconsolidation, namely: the labilization of the reactivated memory and the specificity of the reminder structure. To study this proposal, subjects received two different training sessions on verbal material on Day 1 and Day 2, respectively. Finally, they were tested for the first and second acquired memories on Day 3. It is demonstrated that the human declarative memory fulfills the two requirements that define the process. First, the reactivated memory is impaired by a new learning only when it is given closely after the reminder, revealing that the memory is labilized. Second, the omission of at least one of the reminder's components prevents labilization. Therefore, results show that the new learning fails to produce an amnesic effect on the target memory either when the reminder omits the learned cue or includes the beginning of the reinforcement.

Caveolins in glial cell model systems: from detection to significance.

Glial cells prevail in number and in diversity of cellular phenotypes in the nervous system. They have also gained prominence due to their multiple physiological and pathophysiological roles. Our current knowledge of the asymmetry and heterogeneity of the plasma membrane demands an in depth analysis of the diverse array of membrane microdomains postulated to exist in the context of glial cells. This review focuses and analyzes the studies reported to date on the detection of caveolae membrane rafts and the caveolin family members in glial cell model systems, the conditions leading to changes in their level of expression, and their functional and clinical significance. Outstanding in this work emerge the ubiquitous expression of caveolins, including the typically regarded 'muscle-specific' cav3, in diverse glial cell model systems, their participation in reactive astrogliosis, cancer, and their key relevance to calcium signaling. The knowledge obtained to date demands incorporation of the caveolins and caveolae membrane rafts in our current models on the role of glial cells in heath and neurological disease.

Midazolam disrupts fear memory reconsolidation.

The current research examines the influence of midazolam (MDZ) on memory reconsolidation using a contextual fear paradigm in rats, based on three context-shock training trials (0.7 mA, 3 s). First, we evaluate the effect of MDZ (1 mg/kg, i.p.) injected shortly after the training procedure. Second, we examined the influence of MDZ after a brief exposure (90 s) either in the training context (reactivation procedure) or in a neutral environment (no reactivation procedure) and one day later, freezing behavior was scored when rats were re-exposed to the training environment. Third, we investigate both the effect of MDZ administered at different times following reactivation on fear memory and the persistence of such effect 10 days after reactivation. Finally, we test whether the MDZ effect could be reverted by a single weak training trial (0.2 mA, 3 s) or by the presentation of the same unconditioned stimulus in the absence of the conditioned stimulus as a reminder which proves to induce significant freezing in rats not previously trained. Results show that MDZ interferes with the formation of a contextual fear memory only when administered after the reactivation procedure but not after the training procedure. This interference was effective up to 60 min after reactivation and not at a later time. No spontaneous recovery of freezing behavior was observed 11 days after MDZ injection which was not reverted by a weak training trial and by the unconditioned stimulus alone. All these data support the idea that stimulating GABA A receptor sites via MDZ selectively disrupts the reconsolidation process of a contextual fear memory.

pH regulatory Na/H exchange by Amphiuma red blood cells.

In Amphiuma red blood cells, the Na/H exchanger has been shown to play a central role in the regulation of cell volume following cell shrinkage (Cala, P. M. 1980. Journal of General Physiology. 76:683-708.) The present study was designed to evaluate the existence of pH regulatory Na/H exchange in the Amphiuma red blood cell. The data illustrate that when the intracellular pHi was decreased below the normal value of 7.00, Na/H exchange was activated in proportion to the degree of acidification. Once activated, net Na/H exchange flux persisted until normal intracellular pH (6.9-7.0) was restored, with a half time of approximately 5 min. These observations established a pHi set point of 7.00 for the pH-activated Na/H exchange of Amphiuma red blood cell. This is in contrast to the behavior of osmotically shrunken Amphiuma red blood cells in which no pHi set point could be demonstrated. That is, when activated by cell shrinkage the Na/H exchange mediated net Na flux persisted until normal volume was restored regardless of pHi. In contrast, when activated by cell acidification, the Na/H exchanger functioned until pHi was restored to normal and cell volume appeared to have no effect on pH-activated Na/H exchange. Studies evaluating the kinetic and inferentially, the molecular equivalence of the volume and pHi-induced Amphiuma erythrocyte Na/H exchanger(s), indicated that the apparent Na affinity of the pH activated cells is four times greater than that of shrunken cells. The apparent Vmax is also higher (two times) in the pH activated cells, suggesting the involvement of two distinct populations of the transporter in pH and volume regulation. However, when analyzed in terms of a bisubstrate model, the same data are consistent with the conclusion that both pH and volume regulatory functions are mediated by the same transport protein. Taken together, these data support the conclusion that volume and pH are regulated by the same effector (Na/H exchanger) under the control of as yet unidentified, distinct and cross inhibitory volume and pH sensing mechanisms.

Caveolin isoform expression during differentiation of C6 glioma cells.

Caveolae, a specialized form of lipid rafts, are cholesterol- and sphingolipid-rich membrane microdomains implicated in potocytosis, endocytosis, transcytosis, and as platforms for signal transduction. One of the major constituents of caveolae are three highly homologous caveolin isoforms (caveolin-1, caveolin-2, and caveolin-3). The present study expands the analysis of caveolin isoform expression in C6 glioma cells. Three complementary approaches were used to assess their differential expression during the dibutyryl-cyclic AMP-induced differentiation of C6 cells into an astrocyte-like phenotype. Immunoblotting, conventional RT-PCR, and real-time RT-PCR analysis established the expression of the caveolin-3 isoform in C6 cells, in addition to caveolin-1 and caveolin-2. Similar to the other isoforms, caveolin-3 was associated with light-density, detergent-insoluble caveolae membrane fractions obtained using sucrose-density gradient centrifugation. The three caveolin isoforms display different temporal patterns of mRNA/protein expression during the differentiation of C6 cells. Western blot and real-time RT-PCR analysis demonstrate that caveolin-1 and caveolin-2 are up-regulated during the late stages of the differentiation of C6 cells. Meanwhile, caveolin-3 is gradually down-regulated during the differentiation process. Indirect immunofluorescence analysis via laser-scanning confocal microscopy reveals that the three caveolin isoforms display similar subcellular distribution patterns. In addition, co-localization of caveolin-1/caveolin-2 and caveolin-1/caveolin-3 was detected in both C6 glioma phenotypes. The findings reveal a differential temporal pattern of caveolin gene expression during phenotypic differentiation of C6 glioma cells, with potential implications to developmental and degenerative events in the brain.

Use of Tithonia diversifolia (hemsl) A. Gray in the diet of growing lambs / [Uso de tithonia diversifolia (hemsl) A. Gray na dieta de cordeiros em crescimento]

Two assays were conducted to study the Tithonia diversifolia (Td) plant: (1) chemical analysis and in vitro dry matter digestibility (IVDMD) of plant parts and (2) productive performance of lambs fed a traditional diet or a Td diet (30% of Td plus 70% of the traditional diet). The plant parts studied were leaves (L), leaves and petioles (LP); and leaves, petioles and stems (LPS). Feed intake, weight gain and feed conversion were registered weekly during five weeks of experimentation. The L showed higher (P<0.05) crude protein content (26.7%) than LP and LPS (25.5 and 19.7%, respectively). Crude fiber (11.2%), neutral detergent fiber (45.4%), cellulose (16.9%) and hemicellulose (33.5%) were lower in L than in LP (12.5, 46.7, 18.0 and 35.7%, respectively) and LPS (22.6, 59.2, 27.0 and 43.5%, respectively). The L and LP showed the highest IVDMD (89.2 and 88.2%, respectively vs. 77.2% of LPS). The Td diet resulted in greater feed intake and weight gain and lower feed conversion than the traditional diet. Therefore, Tithonia diversifolia is a forage plant of good quality for lambs which does not affect the productive performance.(AU)

Dois ensaios foram realizados para estudar a planta de Tithonia diversifolia (Td): (1) análise química e digestibilidade in vitro da matéria seca (DIVMS) de partes de plantas e (2) desempenho produtivo de cordeiros alimentados com dieta tradicional ou dieta Td (30% de Td mais 70% da dieta tradicional). As partes vegetais estudadas foram folhas (L), folhas e pecíolos (LP); folhas, pecíolos e caules (LPS). O consumo de ração, o ganho de peso e a conversão alimentar foram registrados semanalmente, durante cinco semanas de experimentação. O L apresentou maior (P<0,05) conteúdo de proteína bruta (26,7%) que o LP e o LPS (25,5 e 19,7%, respectivamente). Fibra bruta (11,2%), fibra em detergente neutro (45,4%), celulose (16,9%) e hemicelulose (33,5%) foram menores em L do que em LP (12,5, 46,7, 18,0 e 35,7%, respectivamente) e LPS (22,6, 59,2, 27,0 e 43,5%, respectivamente). O L e o LP apresentaram o maior DIVMS (89,2 e 88,2%, respectivamente vs. 77,2% do LPS). A dieta Td resultou em maior consumo de ração e maior ganho de peso e menor conversão alimentar que a dieta tradicional. Portanto, Tithonia diversifolia é uma planta forrageira de boa qualidade para cordeiros que não afeta o desempenho produtivo.(AU)

Octreotide therapy of large-volume refractory AIDS-associated diarrhea: a randomized controlled trial.

OBJECTIVE: To compare the effect of octreotide (a long-acting somatostatin analog) to that of antidiarrheal therapy plus placebo on large-volume refractory AIDS-associated diarrhea. DESIGN: A randomized controlled trial. SETTING: Referral-based clinic and hospital in a tertiary care center. PATIENTS: Twenty male patients with AIDS and refractory diarrhea, with stool volume > 1000 ml/day who failed to improve after initial supportive management. All patients finished the study. INTERVENTIONS: Patients were randomly given either octreotide in doses of 100, 200 and 300 micrograms subcutaneously every 8 h, or high doses of loperamide and diphenoxylate orally plus placebo subcutaneously for 10 days. MAIN OUTCOME MEASURES: Bowel movements and stool volume were registered before and every day after treatment by the patients themselves and the nursing personnel. RESULTS: Patients from both groups were similar for age, time of AIDS diagnosis, duration of diarrhea and etiology. Baseline mean bowel movements per day (9.4 +/- 2.8 in the octreotide group versus 10 +/- 3.1 in controls) and baseline mean stool volume (2753 +/- 840 versus 2630 +/- 630 ml/day, respectively) were similar in both groups before therapy (P < 0.05). Mean bowel movements per day after 10 days of therapy was 2.1 +/- 1.6 in the octreotide group versus 7 +/- 3 in controls (P < 0.05). Mean stool volume after 10 days of therapy was 485 +/- 480 in the octreotide group versus 1080 +/- 420 ml/day in controls (P < 0.05). Complete response (stool volume < 250 ml/day) was observed in two patients from the octreotide group and none from controls; partial response (decrease > 50% in stool volume) in four and two; and no response (decrease < 50% or no change) in four and eight (P < 0.05), respectively. Side-effects occurred in eight out of 10 octreotide patients and three out of 10 controls (P < 0.05), but none were significant to result in discontinuation of medication. CONCLUSION: Octreotide proved to be superior to conventional therapy in this short-term treatment of large-volume refractory AIDS-associated diarrhea.

Cortisol and the hypercholesterolemia of pregnancy and labor.

Lipids and lipoproteins are known to increase substantially during pregnancy and to decrease rapidly after delivery. The factors responsible for the changes have not been identified, however, they could be related to changes in one or more of the endocrine hormones. Since studies relating lipid and lipoprotein changes to cortisol or estradiol concentrations have not been made, we sought to perform such a study. For this study, we measured cholesterol, HDL-C, VLDL/LDL-C, cortisol, and estradiol concentrations from early gestation through delivery in 32 normal pregnant women. During the course of pregnancy, cholesterol increased from 145 to 211 mg/dl (45%); plasma cortisol increased from 8.6 to 17.8 micrograms/dl (107%); and urinary cortisol increased from 0.10 to 0.177 microgram/mg of creatinine (72%). Further significant increases in cholesterol (256 mg/dl, P less than 0.005) and cortisol (77.6 micrograms/dl, P less than 0.001) occurred during labor, and both decreased after delivery. Pooled correlations were calculated and both cholesterol and VLDL/LDL-cholesterol concentrations were found to be related to plasma cortisol as well as to urinary cortisol (P less than 0.001). Plasma estradiol concentrations increased during pregnancy, but not during labor. The results suggest that the increases in cholesterol during pregnancy and labor could be due, in part, to the metabolic and stress-related increases in cortisol. The studies also suggest that both pregnancy and labor and delivery might be useful "natural" models for studying hormonal mechanisms involved in lipid and lipoprotein metabolism.

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

Juvenile myoclonic epilepsy (JME) may be linked to the BF and HLA loci on human chromosome 6.

Although certain forms of epilepsy have long been suspected to be inherited, heterogeneity has made it difficult to find the genes responsible for any subtypes. We found that families ascertained through patients with juvenile myoclonic epilepsy show linkage with the BF and HLA loci on human chromosome 6. There is some evidence that the locus may be outside the HLA complex and no evidence as yet of an association with any allele of the HLA complex.

Opioid action on response level to a danger stimulus in the crab (Chasmagnathus granulatus).

When a passing shadow is presented to the crab (Chasmagnathus granulatus), an escape response is elicited that habituates after repeated stimulation. Results of previous papers suggest that this habituation might be mediated by endogenous opiates, entailing the postulate that opiates may inhibit the response to a danger stimulus. This contention is tested herein. Two trials (T1, T2) of shadow stimulation were given 30 min apart, and the response activity was recorded. In Experiment 1 a range of morphine doses (0, 25, 50, 75, and 100 micrograms/g) were injected into crabs immediately after T1. Analysis of the M response values showed a morphine dose-dependent reduction in the crab's reactivity to the danger stimulus in T2. In Experiment 2, groups of crabs were injected with 1 of 4 solutions; saline, 70 micrograms/g morphine, 70 micrograms/g morphine plus 1.6 micrograms/g naloxone. Results suggest that morphine acts through an opiate receptor to inhibit the crab's response level to a danger stimulus. Three possible mechanisms of the morphine effect are discussed, and the most viable one suggests a central site of action.

Nonhabituation processes affect stimulus specificity of response habituation in the crab Chasmagnathus granulatus.

The escape response of the crab (Chasmagnathus granulatus) habituates to repeated electrical shock (SH) or to the presentation of a screen moving horizontally (H) or vertically (V) overhead. Stimulus specificity of the habituated response is shown 24 hr after training but not after either 90 or 45 min. This disruption at short intervals is explained by a transient effect that arises from training: SH training and H training attenuate and V training enhances reactivity. The attenuating effect of H training is reduced by naloxone when administered before but not after training. The results support the hypothesis that during the crab's training two types of processes takes place: a stimulus-specific, long-lasting habituation process that promotes between-sessions response habituation and a nonhabituation process that promotes nonstimulus-specific, less persistent changes of behavior that involve either response habituation or response sensitization. The effect of H training seems to be mediated by an opioid mechanism through secondary activation.

Acute administration of a permeant analog of cAMP and a phosphodiesterase inhibitor improve long-term habituation in the crab Chasmagnathus.

A shadow passing overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus that habituates promptly and for a long period. Robust retention is shown at 24 h after 15 trials of shadow presentation or at 120 h after 30 trials, but no significant retention is disclosed at 24 h after 5 trials or at 72 h after 15. A cocktail of the cAMP membrane permeable analog 8-(4-chlorophenylthio)-cAMP (CPT-cAMP), plus the phosphodiesterase inhibitor isobutyl methylxanthine (IBMX), was given by systemic administration. Pretraining injection of the cocktail (25 or 50 microM, 15 min before a 5-trial session) failed to affect short-term habituation, but induced significant retention when tested at 24 h. This facilitatory effect was not shown when a lower dose (5 microM) was used. A post-training injection of 25 microM, immediately after a 5- or 15-trial session, induced retention when tested at 24 or 72 h, respectively. Thus, the administration of CPT-cAMP + IBMX during acquisition of a habituated response or immediately after, improves long-term habituation, a result supporting the view that an increase in the cAMP level is one of the steps in long-term memory consolidation.

Danger stimulus-induced analgesia in the crab Chasmagnathus granulatus.

When a danger stimulus (a passing shadow) is presented to the crab Chasmagnathus granulatus, an escape response is elicited that habituates after repeated stimulation. Results from previous work suggest that this habituation might be mediated by endogenous opiates and, thus, that after an habituation session an analgesic effect on the response to a painful stimulus should be found. The purpose here was to test this contention. Each crab was lodged in an actometer where two 2-trial sessions with electrical shock stimulation were given (SS1, SS2), the intersession interval being 60 or 105 min, and the response activity recorded. In some experiments, repeated shadow stimulation was inserted during the interval, and the response activity also recorded. In Expt. 1, shadow sessions of 15 and 30 trials were tested and a significant decrease of the reactivity to the shock was only shown with 30 trials. In Expt. 2, crabs were immediately injected after SS1 with distilled water (d.w.) or naloxone (NX) (3.2 micrograms/g), and a shadow session of 30 trials was given to half of the d.w. animals and to half of the NX ones. NX injected crabs showed an increased responsiveness to the danger stimulus during the shadow session but no inhibitory effect on pain reactivity to the subsequent painful stimulus. Issues concerning dependence of the analgesia on danger stimulus iteration and on stimulus controllability, as well as the opioid nature of the analgesia, are discussed.

Vestibular-oculomotor interaction in cat eye-head movements.

When cats make slow scanning head movements, intersaccadic counterrotary eye movements are driven by the vestibulo-ocular reflex, but reset or forward saccades are not directly affected by vestibular afference. When the movements are rapid (approximately 200 deg./sec), large (greater than 40 degrees), and executed in single step shifts gaze (whether in the dark or during visual fixation shifts between known targets), there is no longer any clear vestibular effect on any eye movements during the gaze shift. The vestibulo-ocular reflex is active only at the beginning of head rotation and again at its termination as the gaze reaches its goal, even in the absence of vision. It is postulated that head-in-space and eye-in-orbit movements are perfectly monitored to adjust the amplitude of gaze shifts, despite the lack of overt vestibular effects on eye movements.