Prosomeric Hypothalamic Distribution of Tyrosine Hydroxylase Positive Cells in Adolescent Rats.

Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region lies ventrally within the diencephalon, which includes preoptic, anterior, tuberal, and mamillary anteroposterior regions, and sometimes identifying dorsal, intermediate, and ventral hypothalamic partitions. This model is weak in providing little or no experimentally corroborated causal explanation of such subdivisions. In contrast, the modern prosomeric model uses different axial assumptions based on the parallel courses of the brain floor, alar-basal boundary, and brain roof (all causally explained). This model also postulates that the hypothalamus and telencephalon jointly form the secondary prosencephalon, separately from and rostral to the diencephalon proper. The hypothalamus is divided into two neuromeric (transverse) parts called peduncular and terminal hypothalamus (PHy and THy). The classic anteroposterior (AP) divisions of the columnar hypothalamus are rather seen as dorsoventral subdivisions of the hypothalamic alar and basal plates. In this study, we offered a prosomeric immunohistochemical mapping in the rat of hypothalamic cells expressing tyrosine hydroxylase (TH), which is the enzyme that catalyzes the conversion of L-tyrosine to levodopa (L-DOPA) and a precursor of dopamine. This mapping was also combined with markers for diverse hypothalamic nuclei [agouti-related peptide (Agrp), arginine vasopressin (Avp), cocaine and amphetamine-regulated transcript (Cart), corticotropin releasing Hormone (Crh), melanin concentrating hormone (Mch), neuropeptide Y (Npy), oxytocin/neurophysin I (Oxt), proopiomelanocortin (Pomc), somatostatin (Sst), tyrosine hidroxilase (Th), and thyrotropin releasing hormone (Trh)]. TH-positive cells are particularly abundant within the periventricular stratum of the paraventricular and subparaventricular alar domains. In the tuberal region, most labeled cells are found in the acroterminal arcuate nucleus and in the terminal periventricular stratum. The dorsal retrotuberal region (PHy) contains the A13 cell group of TH-positive cells. In addition, some TH cells appear in the perimamillary and retromamillary regions. The prosomeric model proved useful for determining the precise location of TH-positive cells relative to possible origins of morphogenetic signals, thus aiding potential causal explanation of position-related specification of this hypothalamic cell type.

Increased cortisol levels caused by acute resistance physical exercise impair memory and learning ability.

Acute physical exercise works as an activator of the responses of the human organism to stress. This is based on the activation of the hypothalamic-pituitary-adrenal (HPA) axis, affecting physical, physiological and psychological levels. This study aimed to analyse the effects of a single bout of high-intensity resistance exercise on cognitive-behavioural responses: visuo-spatial path learning and memory, as well as physiological responses (salivary cortisol levels). Nineteen healthy male military-trained powerlifting subjects were tested in a within-subject design on two experimental days with an interval of 48 h. The stress and cognitive variables were measured by cortisol levels and Ruff-Light trail-learning test (RULIT) test scores, respectively. The results showed the immediate influence of acute exercise on cortisol, with significantly higher cortisol levels found in subjects after completion of the acute resistance exercise. In addition, this study found a significant deterioration of memory and learning ability after a dose of intense resistance exercise. In conclusion, the study highlights the relative effects of resistance exercise on cortisol and cognitive performance depending on the intensity and type of the exercise, the moment of measurement and the cerebral areas implicated.

Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Moreover, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and the activity of the mTOR pathway, which is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by drug priming and social stress. Reinstatement of cocaine CPP paralleled an increasing trend in D3R and dopamine transporter (DAT) levels in the BLA. Social stress, but not drug-induced reactivation of cocaine memories, was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), which was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitant with cocaine CPP reactivation, a diminution in mTOR phosphorylation (activation) in the BLA and DG occurred, which was inhibited by D3R blockade in both nuclei before the social stress episode and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while supporting a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicate that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli.

The Mediator Role of Feelings of Guilt in the Process of Burnout and Psychosomatic Disorders: A Cross-Cultural Study.

Burnout was recently declared by WHO as an "occupational phenomenon" in the International Classification of Diseases 11th revision (ICD-11), recognizing burnout as a serious health issue. Earlier studies have shown that feelings of guilt appear to be involved in the burnout process. However, the exact nature of the relationships among burnout, guilt and psychosomatic disorders remains unclear. The purpose of this study was to investigate the mediator role of feelings of guilt in the relationship between burnout and psychosomatic disorders, and perform a cross-cultural validation of the multi-dimensional model by Gil-Monte in two samples of teachers (Portuguese vs. Spanish). The study sample was composed of 1,266 teachers, 1,062 from Spain, and 204 from Portugal. Burnout was measured by the Spanish Burnout Inventory. Hypotheses were tested together in a path model. The results obtained provide empirical evidence for the mediator role of guilt in the relationship between the Burnout syndrome and psychosomatic disorders in the sample of teachers from Spain and Portugal, and they contribute to the empirical validation of the model by Gil-Monte. The results indicate that guilt should be incorporated as a symptom of burnout in order to identify individuals affected by burnout and profiles or types of burnout to differentiate it from other pathologies like depression.

Hypothalamic Crh/Avp, Plasmatic Glucose and Lactate Remain Unchanged During Habituation to Forced Exercise.

It has been demonstrated that physical activity contributes to a healthier life. However, there is a knowledge gap regarding the neural mechanisms producing these effects. One of the keystones to deal with this problem is to use training programs with equal loads of physical activity. However, irregular motor and stress responses have been found in murine exercise models. Habituation to forced exercise facilitates a complete response to a training program in all rodents, reaching the same load of physical activity among animals. Here, it was evaluated if glucose and lactate - which are stress biomarkers - are increased during the habituation to exercise. Sprague-Dawley rats received an 8-days habituation protocol with progressive increments of time and speed of running. Then, experimental and control (non-habituated) rats were subjected to an incremental test. Blood samples were obtained to determine plasmatic glucose and lactate levels before, immediately after and 30 min after each session of training. Crh and Avp mRNA expression was determined by two-step qPCR. Our results revealed that glucose and lactate levels are not increased during the habituation period and tend to decrease toward the end of the protocol. Also, Crh and Avp were not chronically activated by the habituation program. Lactate and glucose, determined after the incremental test, were higher in control rats without previous contact with the wheel, compared with habituated and wheel control rats. These results suggest that the implementation of an adaptive phase prior to forced exercise programs might avoid non-specific stress responses.

Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories.

Morphine is thoroughly used for pain control; however, it has a high addictive potential. Opioid liposome formulations produce controlled drug release and have been thoroughly tested for pain treatment although their role in addiction is still unknown. This study investigated the effects of free morphine and morphine encapsulated in unilamellar and multilamellar liposomes on antinociception and on the expression and extinction of the positive and negative memories associated with environmental cues. The hot plate test was used to measure central pain. The rewarding effects of morphine were analyzed by the conditioned-place preference (CPP) test, and the aversive aspects of naloxone-precipitated morphine withdrawal were evaluated by the conditioned-place aversion (CPA) paradigm. Our results show that encapsulated morphine yields prolonged antinociceptive effects compared with the free form, and that CPP and CPA expression were similar in the free- or encapsulated-morphine groups. However, we demonstrate, for the first time, that morphine encapsulation reduces the duration of reward and aversive memories, suggesting that this technological process could transform morphine into a potentially less addictive drug. Morphine encapsulation in liposomes could represent a pharmacological approach for enhancing extinction, which might lead to effective clinical treatments in drug addiction with fewer side effects.

Age and gender effects on the prevalence of poor sleep quality in the adult population / Efecto de la edad y el sexo sobre la prevalencia de una pobre calidad del sueño en población adulta

Objective: Sleep quality has a significant impact on health and quality of life and is affected, among other factors, by age and sex. However, the prevalence of problems in this area in the general population is not well known. Therefore, our objective was to study the prevalence and main characteristics of sleep quality in an adult population sample. Methods: 2,144 subjects aged between 43 and 71 years belonging to the Murcia (Spain) Twin Registry. Sleep quality was measured by self-report through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression models were used to analyse the results. Results: The prevalence of poor sleep quality stands at 38.2%. Univariate logistic regression analyses showed that women were almost twice as likely as men (OR: 1.88; 95% confidence interval [95%CI]: 1.54 to 2.28) to have poor quality of sleep. Age was directly and significantly associated with a low quality of sleep (OR: 1.05; 95%CI: 1.03 to 1.06). Conclusions: The prevalence of poor sleep quality is high among adults, especially women. There is a direct relationship between age and deterioration in the quality of sleep. This relationship also appears to be more consistent in women (AU)

Objetivo: La calidad del sueño tiene una incidencia notable en la salud y en la calidad de vida, y a su vez se ve afectada, entre otros factores, por la edad y el sexo. Sin embargo, la prevalencia de problemas en este ámbito en la población general no es bien conocida. Por ello, nuestro objetivo fue estudiar la prevalencia y las características de la calidad del sueño en una muestra de población adulta. Métodos: 2144 personas de edades comprendidas entre 43 y 71 años pertenecientes al Registro de Gemelos de Murcia. La calidad del sueño se determinó por autoinforme mediante el índice de calidad del sueño de Pittsburgh. Se utilizaron modelos de regresión logística para el análisis de los resultados. Resultados: La prevalencia de una pobre calidad del sueño se sitúa en el 38,2%. Los análisis de regresión logística univariados mostraron que las mujeres prácticamente doblaban (odds ratio [OR]: 1,88; intervalo de confianza del 95% [IC95%]: 1,54-2,28) la probabilidad de tener una pobre calidad del sueño con respecto a los hombres. La edad se asocia de manera directa y significativa con una baja calidad del sueño (OR: 1,05; IC95%: 1,03-1,06). Conclusiones: La prevalencia de una pobre calidad del sueño es alta en la población adulta, en especial en las mujeres. Existe una relación directa entre la edad y el deterioro de la calidad del sueño. Esta relación también parece ser más consistente en las mujeres (AU)

Age and gender effects on the prevalence of poor sleep quality in the adult population.

OBJECTIVE: Sleep quality has a significant impact on health and quality of life and is affected, among other factors, by age and sex. However, the prevalence of problems in this area in the general population is not well known. Therefore, our objective was to study the prevalence and main characteristics of sleep quality in an adult population sample. METHODS: 2,144 subjects aged between 43 and 71 years belonging to the Murcia (Spain) Twin Registry. Sleep quality was measured by self-report through the Pittsburgh Sleep Quality Index (PSQI). Logistic regression models were used to analyse the results. RESULTS: The prevalence of poor sleep quality stands at 38.2%. Univariate logistic regression analyses showed that women were almost twice as likely as men (OR: 1.88; 95% confidence interval [95%CI]: 1.54 to 2.28) to have poor quality of sleep. Age was directly and significantly associated with a low quality of sleep (OR: 1.05; 95%CI: 1.03 to 1.06). CONCLUSIONS: The prevalence of poor sleep quality is high among adults, especially women. There is a direct relationship between age and deterioration in the quality of sleep. This relationship also appears to be more consistent in women.

Hábitos de consumo de drogas y percepción sobre los efectos en salud y rendimiento académico en estudiantes de Psicología en la Universidad de Huelva / No disponible

El objetivo del trabajo es describir las prevalencias y las relaciones entre las diferentes drogas en estudiantes universitarios. Además conocer la percepción que tienen los estudiantes sobre los efectos de las drogas en el rendimiento académico y en la salud. La muestra está compuesta por 153 estudiantes de psicología de la Universidad de Huelva. Los datos de consumo y percepción se recogen mediante un cuestionario, anónimo y voluntario. Nuestros resultados ponen de manifiesto que las sustancias más consumidas y de inicio más temprano son el alcohol, el tabaco y el cannabis, por tanto, se confirman las tendencias encontradas en jóvenes. Del mismo modo, se confirma el patrón de policonsumo en un 60,78% de la muestra. El consumo de tabaco se inicia antes que el del alcohol o cannabis, y cuanto antes se inicia en el consumo de tabaco, antes también se inicia en el consumo de otras sustancias. Según sean las sustancias combinadas, se hallan diferencias en la edad de inicio del alcohol y en la cantidad de cigarrillos de tabaco. Se comienza a consumir alcohol antes si los que beben también fuman. Los que fuman más cigarros son los que combinan el tabaco con alguna otra droga ilegal distinta al cannabis. Con respecto a la percepción sobre el efecto del consumo de drogas, aquellos que consumen alcohol, tabaco y cannabis, consideran que las drogas afectan menos al rendimiento académico que los no consumidores o consumidores dedrogas legales

The aim of this study is to describe the prevalence and relationships between different drugs among college students, as well as getting to know the perception of students about the effects of drugs on academic performance and health. The sample consists of 153 psychology students from the University of Huelva. The consumption and perception data are collected by an anonymous and voluntary questionnaire. Our results show that the most widely-consumed substances with earliest onset are alcohol, tobacco and cannabis, thus confi rming the trends found in young people. Similarly,polyconsumption is confi rmed with a percentage of 60.78% of the sample. Tobacco consumption starts earlier than alcohol or cannabis, and the sooner people start to consume tobacco, the sooner the consumption of other substances starts. Depending on the substances combined, there are differences in the age of onset of alcohol and the quantity of tobacco cigarettes. Thus, if those who drink also smoke, theage of onset of alcohol use is earlier. Those who smoke most cigarettes are the ones who combine tobacco with any illegal drug other than cannabis. With regard to perception of the effect of drug use, students who use alcohol, cannabis and tobacco consider that drugs affect academic performance less than non-users or consumers of legal drugs

Adolescent pre-exposure to ethanol and 3,4-methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug-induced reinstatement.

Many adolescents often take ethanol (EtOH) in combination with 3,4-methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre-exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre-exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre-treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre-exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups with a priming dose of 2.5 mg/kg of MDMA, in the groups pre-exposed to EtOH or MDMA alone with a priming dose of 1.25 mg/kg, and in the groups pre-treated with MDMA alone with a priming dose of 0.625 mg/kg. Pre-treatment during adolescence with MDMA or EtOH induced long-term changes in the level of biogenic amines [dihydroxyphenyl acetic acid, homovanillic acid, dopamine turnover, serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the striatum, and 5-HT and 5-HIAA in the cortex] after the first reinstatement test, although these effects depended on the dose used during conditioning. These results suggest that exposure to EtOH and MDMA during adolescence reinforces the addictive properties of MDMA.

Social experiences affect reinstatement of cocaine-induced place preference in mice.

RATIONALE: Drug addiction is a multifactorial disorder resulting from an interaction between genetic and environmental factors, and negative and positive environmental conditions may increase or reduce, respectively, vulnerability to drug addiction. OBJECTIVES: The influence of different social experiences on the acquisition, extinction, and reinstatement of a cocaine-induced conditioned place preference (CPP) was evaluated. METHODS: In experiment 1, adolescent and adult male OF1 mice housed under four different conditions (grouped, isolated, crowded, and cohabitating with a female) were conditioned with 50, 12.5, or 3.125 mg/kg of cocaine. All mice underwent extinction sessions until the CPP was extinguished. The effects of cocaine priming injections on the reinstatement of CPP were then evaluated. In experiment 2, the effect of different social experiences on the maintenance and reinstatement of cocaine-CPP in adult mice was studied. RESULTS: Although housing conditions did not affect the acquisition of cocaine-CPP, it did modify reinstatement after extinction. Adolescent mice living in crowded conditions or cohabitating with a female did not present reinstatement after cocaine priming. Similarly, neither isolated adult mice nor adults cohabitating with a female presented reinstatement. In grouped adult mice, isolation after acquisition of the CPP and social defeat before reinstatement increased the vulnerability to reinstatement induced by cocaine priming. Conversely, both exposure to females and a brief social interaction undermined cocaine-induced reinstatement. CONCLUSIONS: Social experiences modify vulnerability to reinstatement, acting as prevention or risk factors in the development of drug addiction.

Rewarding effects and reinstatement of MDMA-induced CPP in adolescent mice.

Although the rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in self-administration and conditioned place preference (CPP) procedures, its addictive potential (ie, the vulnerability to relapse, measured by its ability to induce reinstatement of an extinguished response), remains poorly understood. In this study, the effects of MDMA (5, 10, and 20 mg/kg) on the acquisition, extinction and reinstatement of CPP were evaluated in mice, using two different protocols during acquisition of CPP. In the first experiment, animals were trained using a two-session/day schedule (MDMA and saline for 4 consecutive days), whereas in the second experiment, they were trained using an alternating day schedule (MDMA and saline each 48 h). After extinction, the ability of drug priming to reinstate CPP was evaluated. In Experiment 1, MDMA did not significantly increase the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, although the preference was evident a week afterwards, lasting between 2 and 21 weeks. No reinstatement was observed after MDMA priming. In Experiment 2, all doses produced CPP in Post-C, which lasted between 1 and 4 weeks. MDMA induces reinstatement at doses up to 4 times lower than those used in conditioning. The analyses of brain monoamines revealed that the daily schedule of treatment induces a non-dose-dependent decrease in dopamine and serotonin (5-HT) in the striatum, whereas the alternating schedule produces a dose-dependent decrease of 5-HT in the cortex. These results demonstrate that MDMA produces long-lasting rewarding effects and reinstatement after extinction, suggesting the susceptibility of this drug to induce addiction.

Effects of NMDA receptor antagonists (MK-801 and memantine) on the acquisition of morphine-induced conditioned place preference in mice.

Several studies have shown that the systemic administration of a variety of N-methyl-D-aspartate (NMDA) receptor antagonists can block the development or expression of conditioned place preference (CPP) induced by rewarding drugs such as morphine. In the present study, we examined the effects of different doses of two non-competitive NMDA receptor antagonists, MK-801 (0.1, 0.2 and 0.3 mg/kg) and memantine (2.5, 5, 10, 20 and 40 mg/kg), in CPP induced by 40 mg/kg of morphine in male mice. The CPP was carried out with an unbiased procedure in terms of initial spontaneous preference. Animals received the different doses of drugs in the conditioning sessions. MK-801 and memantine, at all doses used, produced neither place preference nor place aversion, but the higher doses of memantine (20 and 40 mg/kg) were able to completely block morphine-induced CPP. The present data show that the NMDA receptor antagonists MK-801 and memantine have no reinforcing properties but memantine is capable of preventing the acquisition of morphine-induced CPP. These results suggest that the development of morphine-induced CPP may be closely related to NMDA receptors and that the glutamatergic system can modulate opiate reward.