RESUMEN
The relevance of vasopressin (AVP) of magnocellular origin to the regulation of the endocrine stress axis and related behaviour is still under discussion. We aimed to obtain deeper insight into this process. To rescue magnocellular AVP synthesis, a vasopressin-containing adeno-associated virus vector (AVP-AAV) was injected into the supraoptic nucleus (SON) of AVP-deficient Brattleboro rats (di/di). We compared +/+, di/di, and AVP-AAV treated di/di male rats. The AVP-AAV treatment rescued the AVP synthesis in the SON both morphologically and functionally. It also rescued the peak of adrenocorticotropin release triggered by immune and metabolic challenges without affecting corticosterone levels. The elevated corticotropin-releasing hormone receptor 1 mRNA levels in the anterior pituitary of di/di-rats were diminished by the AVP-AAV-treatment. The altered c-Fos synthesis in di/di-rats in response to a metabolic stressor was normalised by AVP-AAV in both the SON and medial amygdala (MeA), but not in the central and basolateral amygdala or lateral hypothalamus. In vitro electrophysiological recordings showed an AVP-induced inhibition of MeA neurons that was prevented by picrotoxin administration, supporting the possible regulatory role of AVP originating in the SON. A memory deficit in the novel object recognition test seen in di/di animals remained unaffected by AVP-AAV treatment. Interestingly, although di/di rats show intact social investigation and aggression, the SON AVP-AAV treatment resulted in an alteration of these social behaviours. AVP released from the magnocellular SON neurons may stimulate adrenocorticotropin secretion in response to defined stressors and might participate in the fine-tuning of social behaviour with a possible contribution from the MeA.
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Núcleo Supraóptico/metabolismo , Vasopresinas/metabolismo , Hormona Adrenocorticotrópica/genética , Animales , Núcleo Basal de Meynert/metabolismo , Encéfalo/metabolismo , Corticosterona/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Brattleboro , Conducta Social , Vasopresinas/fisiologíaRESUMEN
Glutamatergic neurons, characterized by vesicular glutamate transporters (VGluT1-3) provide the main excitation in the brain. Their disturbances have been linked to various brain disorders, which could be also modeled by the contextual fear test in rodents. We aimed to characterize the participation of VGluT3 in the development of contextual fear through its contribution to hypothalamic-pituitary-adrenocortical axis (HPA) regulation using knockout (KO) mice. Contextual fear conditioning was induced by foot shock and mice were examined 1 and 7 d later in the same environment comparing wild type with KO. Foot shock increased the immobility time without context specificity. Additionally, foot shock reduced open arm time in the elevated plus maze (EPM) test, and distance traveled in the open field (OF) test, representing the generalization of fear. Moreover, KO mice spent more time with freezing during the contextual fear test, less time in the open arm of the EPM, and traveled a smaller distance in the OF, with less entries into the central area. However, there was no foot shock and genotype interaction suggesting that VGluT3 does not influence the fear conditioning, rather determines anxiety-like characteristic of the mice. The resting hypothalamic CRH mRNA was higher in KO mice with reduced stressor-induced corticosterone elevations. Immunohistochemistry revealed the presence of VGluT3 positive fibers in the paraventricular nucleus of hypothalamus, but not on the hypophysis. As a summary, we confirmed the involvement of VGluT3 in innate fear, but not in the development of fear memory and generalization, with a significant contribution to HPA alterations. Highlights VGluT3 KO mice show innate fear without significant influence on fear memory and generalization. A putative background is the higher resting CRH mRNA level in their PVN and reduced stress-reactivity.
Asunto(s)
Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Miedo/fisiología , Memoria/fisiología , Sistemas de Transporte de Aminoácidos Acídicos/genética , Animales , Condicionamiento Clásico/fisiología , Corticosterona/sangre , Hipotálamo/metabolismo , Masculino , Ratones , Ratones Noqueados , Neuronas/metabolismoRESUMEN
Laboratory diagnostics is especially important in the diagnosis of certain diseases. We compared manual measurements results to laboratory normal values. In some cases, these values depend on the gender and age as well. In the case of alkaline phosphatase, it is rarely considered that reference values change over life periods. Unfortunately, during the daily practice we do not always take into account of the changes with aging. This is especially true if the laboratory does not specify the age related normal values. Another problem that we mostly focus on the results exceeding the normal values, and do not pay enough attention to the low values. Of course, these results should be put in the context of the clinical picture and other diagnostic test results. We would like to draw attention to the measuring of alkaline phosphatase and the differential diagnosis for low serum activity. Orv Hetil. 2017; 158(26): 1003-1007.
Asunto(s)
Fosfatasa Alcalina/sangre , Hipofosfatasia/diagnóstico , Diagnóstico Diferencial , Humanos , Hipofosfatasia/sangre , Fosfato de Piridoxal/sangreRESUMEN
Vasopressin, a nonapeptide, signaling both as hormone in the blood and neuromodulator/neurotransmitter in the brain is considered to be causally involved in the pathological changes underlying anxiety and depression. In the present review we summarize experimental data obtained with Brattleboro rats as a model of congenital vasopressin-deficiency to test the hypothesis that central vasopressin signaling contributes to anxiety- and depression-like behavior. Male, female and lactating rats were studied. We focused on the paraventricular nucleus of the hypothalamus (PVN) and the septum, two brain areas in which vasopressin is proposed to control the endocrine and behavioral stress response, respectively. The presented data support the hypothesis that the behavioral changes seen in these rats are brought about by an altered vasopressin signaling at the brain level. Whereas vasopressin synthesized and released within the hypothalamus is primarily involved in endocrine regulation, vasopressin signaling in other brain areas may contribute to anxiety- and depression-like behavioral parameters. Further studies in this context might focus particularly on the interplay between extra-hypothalamic brain areas such as the septum and the medial amygdala.
Asunto(s)
Conducta Animal/fisiología , Estrés Psicológico/metabolismo , Vasopresinas/metabolismo , Animales , Ansiedad/metabolismo , Encéfalo/metabolismo , Depresión/metabolismo , Femenino , Lactancia , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas BrattleboroRESUMEN
Stress and related disorders are in the focus of interest and glutamate is one of the most important neurotransmitters that can affect these processes. Glutamatergic neurons are characterized by vesicular glutamate transporters (VGluT1-3) among which vGluT3 is unique contributing to the non-canonical, neuromodulatory effect of glutamate. We aimed to study the role of vGluT3 in stress axis regulation and related anxiety during the early postnatal period using knockout (KO) mice with special focus on sex differences. Anxiety was explored on postnatal day (PND) 7-8 by maternal separation-induced ultrasonic vocalization (USV). Stress-hormone levels were detected 60 min after intraperitoneal lipopolysaccharide (LPS) injection 7 days later. Both genotypes gained weight, but on PND 14-15 KO mice pups had smaller body weight compared to wild type (WT). vGluT3 KO mice reacted to an immune stressor with enhanced adrenocorticotropin (ACTH) and corticosterone secretion compared to WT. Although there was a tendency for enhanced anxiety measured by more emitted USV, this did not reach the level of significance. The only sex-related effect was the enhanced corticosterone reactivity in male pups. For the HPA axis regulation in neonates vGluT3 expression seems to be dispensable under basal conditions, but is required for optimal response to immune stressors, most probably through an interaction with other neurotransmitters. Disturbance of the fine balance between these systems may result in a borderline enhanced anxiety-like behavior in vGluT3 KO pups.
Asunto(s)
Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Ansiedad/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Privación Materna , Sistema Hipófiso-Suprarrenal/metabolismo , Sistemas de Transporte de Aminoácidos Acídicos/genética , Animales , Animales Recién Nacidos , Corticosterona/metabolismo , Femenino , Ácido Glutámico/metabolismo , Masculino , Ratones , Ratones Noqueados , Neuronas/metabolismo , Vocalización AnimalRESUMEN
Both animal and human studies suggest that in adulthood, plasma vasopressin level correlates well with anxiety. Little is known about the mood regulation during the perinatal period. Here, we aim to investigate the influence of vasopressin on anxiety during the early postnatal age. As a sign of distress, rat pups emit ultrasonic vocalizations (USVs) when they are separated from their mother. This USV was detected in 7- to 8-day-old vasopressin-deficient Brattleboro pups, and they were compared to their heterozygote littermates and wild-type pups. The results were confirmed by V1b antagonist treatment (SSR149415 10 mg/kg ip 30 min before test) in wild-types. Chlordiazepoxide (3 mg/kg ip 30 min before test)-an anxiolytic-was used to test the interaction with the GABAergic system. At the end of the test, stress-hormone levels were measured by radioimmunoassay. Vasopressin-deficient pups vocalized substantially less than non-deficient counterparts. Treatment with V1b antagonist resulted in similar effect. Chlordiazepoxide reduced the frequency and duration of the vocalization only in wild-types. Reduced vocalization was accompanied by smaller adrenocorticotropin levels but the level of corticosterone was variable. Our results indicate that the anxiolytic effect of vasopressin deficiency (both genetic and pharmacological) exists already during the early postnatal age. Vasopressin interacts with the GABAergic system. As mood regulation does not go parallel with glucocorticoid levels, we suggest that vasopressin might have a direct effect on special brain areas.
Asunto(s)
Afecto/efectos de los fármacos , Ansiedad/metabolismo , Periodo Posparto/metabolismo , Vasopresinas , Vocalización Animal/efectos de los fármacos , Hormona Adrenocorticotrópica/metabolismo , Animales , Clordiazepóxido/farmacología , Corticosterona/metabolismo , Femenino , Humanos , Ratas , Ratas Brattleboro , Vasopresinas/metabolismo , Vasopresinas/farmacologíaRESUMEN
Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which-among other things-include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine-induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine-tuning of GABAergic and serotonergic function.
Asunto(s)
Arginina Vasopresina/genética , Conducta Impulsiva/fisiología , Lactancia/fisiología , Animales , Arginina Vasopresina/deficiencia , Conducta Animal/fisiología , Cognición/fisiología , Corticosterona/sangre , Femenino , Lactancia/psicología , Conducta Materna/fisiología , Ratas , Ratas Brattleboro , Ratas TransgénicasRESUMEN
Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation) of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers' stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing.
Asunto(s)
Lactancia , Estrés Fisiológico , Estrés Psicológico , Vasopresinas/metabolismo , Animales , Animales Recién Nacidos , Conducta Animal , Femenino , Humanos , Relaciones Madre-HijoRESUMEN
Early mother-infant relationships exert important long-term effects in offspring and are disturbed by factors such as postpartum depression. We aimed to clarify if lack of vasopressin influences maternal behavior paralleled by the development of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro mothers with heterozygous and homozygous normal ones. The following parameters were measured: maternal behavior (undisturbed and separation-induced); anxiety by the elevated plus maze; sucrose and saccharin preference and forced swim behavior. Underlying brain areas were examined by c-fos immunocytochemistry among rest and after swim-stress. In another group of rats, vasopressin 2 receptor agonist was used peripherally to exclude secondary changes due to diabetes insipidus. Results showed that vasopressin-deficient rats spend less time licking-grooming their pups through a centrally driven mechanism. There was no difference between genotypes during the pup retrieval test. Vasopressin-deficient mothers tended to explore more the open arms of the plus maze, showed more preference for sucrose and saccharin and struggled more in the forced swim test, suggesting that they act as less depressive. Under basal conditions, vasopressin-deficient mothers had more c-fos expression in the medial preoptic area, shell of nucleus accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in other structures. In these areas the swim-stress-induced activation was smaller. In conclusion, vasopressin-deficiency resulted in maternal neglect due to a central effect and was protective against depressive-like behavior probably as a consequence of reduced activation of some stress-related brain structures. The conflicting behavioral data underscores the need for more sex specific studies.
Asunto(s)
Conducta Animal/fisiología , Conducta Materna/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas Brattleboro , Vasopresinas/fisiología , Animales , Mapeo Encefálico , Sistema Nervioso Central/metabolismo , Depresión/metabolismo , Depresión/fisiopatología , Depresión/psicología , Femenino , Conducta Materna/psicología , Aprendizaje por Laberinto , Modelos Biológicos , Madres/psicología , Ratas , Ratas Brattleboro/metabolismo , Ratas Brattleboro/fisiología , Ratas Transgénicas , Natación/fisiología , Vasopresinas/genética , Vasopresinas/metabolismoRESUMEN
Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) Brattleboro rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment effects of marketed antipsychotics are similar in di/di rats to those seen in human schizophrenic patients. Chronic subcutaneous administration of aripiprazole (5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.3 mg/kg) or risperidone (0.25 mg/kg) was used for 15 days in control (+/+ Brattleboro) and di/di rats. Social discrimination, social avoidance and prepulse inhibition tests were conducted on day 1, 8 and 15 of the treatment. Vasopressin-deficient rats showed social memory- and sensorimotor gating deficit. All used antipsychotics successfully normalized the reduced prepulse inhibition of di/di animals. However, most were effective only after prolonged treatment. Aripiprazole, clozapine, and olanzapine normalized the social memory deficit, while the effects of haloperidol and risperidone were not unequivocal. All drugs reduced social interest to some extent both in control and in di/di animals, aripiprazole being the less implicated in this regard during the social avoidance test. The restoration of schizophrenia-like behavior by antipsychotic treatment further support the utility of the vasopressin-deficient Brattleboro rat as a good preclinical model. Reduced social interest might be a general side-effect of antipsychotics, and aripiprazole has the most favorable profile in this regard.
Asunto(s)
Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Vasopresinas/deficiencia , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Inyecciones Subcutáneas , Masculino , Ratas , Ratas Brattleboro , Ratas Transgénicas , Esquizofrenia/genética , Conducta Social , Vasopresinas/genéticaRESUMEN
In adults, vasopressin exerts an anxiogenic effect, but less is known about the perinatal period. As a sign of distress, rat pups emit ultrasonic vocalizations when they are separated from their mothers, known as maternal separation-induced ultrasonic vocalization (MS-USV). Previously, reduced MS-USV was reported in 7-8-day-old genetically vasopressin-deficient Brattleboro rats. Here, we aimed to examine the contributing vasopressin receptor (VR) subtypes using Wistar pups. MS-USV was recorded for 10 min, 30 min after vasopressin (V) 1aR, V1bR or V2R antagonist treatment (SR49059, SSR149415, SR121463B; 3, 10 and 30 mg/kg, intraperitoneal). Sedation was studied by the righting reflex and negative geotaxis, and finally, the stress hormone levels were measured by radioimmunoassay. The vasopressin-deficient pups showed decreased MS-USV and adrenocorticotropin levels even after a saline injection, with unchanged corticosterone levels. Thirty mg/kg of V1aR-antagonist increased the corticosterone levels. All V1bR antagonist doses decreased the MS-USV and adrenocorticotropin, while 10 + 10 mg/kg of V1aR and V1bR antagonists decreased MS-USV without influencing the stress hormones. Three mg/kg of V2R antagonist enhanced MS-USV, while 30 mg/kg increased the stress hormone levels. We confirmed that vasopressin deficiency already caused anxiolytic effects in pups. V1bRs are the most important player in connection with their adrenocorticotropin (ACTH)-regulatory role, but a combination of V1aR and V1bR antagonists might be also beneficial through other mechanisms, reducing the possibility of side effects. In contrast, antagonizing the V2Rs may be stressful due to an induction of imbalance in saltwater homeostasis.
RESUMEN
A new, heterogeneous, 4 A molecular sieve-supported copper(ii) catalyst was developed and was used successfully in the A(3) coupling of alkynes, aldehydes and amines under simple reaction conditions.
Asunto(s)
Cobre/química , Pargilina/análogos & derivados , Propilaminas/síntesis química , Aldehídos/química , Alquinos/química , Aminas/química , Catálisis , Química Orgánica/métodos , Pargilina/síntesis química , Pargilina/química , Propilaminas/químicaRESUMEN
Vasopressin can contribute to the development of stress-related psychiatric disorders, anxiety and depression. Although these disturbances are more common in females, most of the preclinical studies have been done in males. We compared female vasopressin-deficient and +/+ Brattleboro rats. To test anxiety we used open-field, elevated plus maze (EPM), marble burying, novelty-induced hypophagia, and social avoidance tests. Object and social recognition were used to assess short term memory. To test depression-like behavior consumption of sweet solutions (sucrose and saccharin) and forced swim test (FST) were studied. The stress-hormone levels were followed by radioimmunoassay and underlying brain areas were studied by c-Fos immunohistochemistry. In the EPM the vasopressin-deficient females showed more entries towards the open arms and less stretch attend posture, drank more sweet fluids and struggled more (in FST) than the +/+ rats. The EPM-induced stress-hormone elevations were smaller in vasopressin-deficient females without basal as well as open-field and FST-induced genotype-differences. On most studied brain areas the resting c-Fos levels were higher in vasopressin-deficient rats, but the FST-induced elevations were smaller than in the +/+ ones. Similarly to males, female vasopressin-deficient animals presented diminished depression- and partly anxiety-like behavior with significant contribution of stress-hormones. In contrast to males, vasopressin deficiency in females had no effect on object and social memory, and stressor-induced c-Fos elevations were diminished only in females. Thus, vasopressin has similar effect on anxiety- and depression-like behavior in males and females, while only in females behavioral alterations are associated with reduced neuronal reactivity in several brain areas.
Asunto(s)
Ansiedad/genética , Encéfalo/patología , Depresión/genética , Estrés Psicológico/genética , Estrés Psicológico/patología , Vasopresinas/deficiencia , Hormona Adrenocorticotrópica/sangre , Animales , Ansiedad/patología , Condicionamiento Operante/fisiología , Modelos Animales de Enfermedad , Femenino , Preferencias Alimentarias/fisiología , Preferencias Alimentarias/psicología , Locomoción/genética , Aprendizaje por Laberinto/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Brattleboro , Ratas Transgénicas , Reconocimiento en Psicología/fisiología , Conducta Social , Natación/psicología , Vasopresinas/genéticaRESUMEN
Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases.
Asunto(s)
Arginina Vasopresina/deficiencia , Epigénesis Genética , Hipocampo/metabolismo , Corteza Prefrontal/metabolismo , Esquizofrenia/metabolismo , Psicología del Esquizofrénico , Acetilación , Animales , Arginina Vasopresina/genética , Modelos Animales de Enfermedad , Femenino , Histonas/metabolismo , Actividad Motora/fisiología , Núcleo Accumbens/metabolismo , Inhibición Prepulso/fisiología , Ratas Brattleboro , Reconocimiento en Psicología/fisiología , Esquizofrenia/genética , Tabique del Cerebro/metabolismo , Conducta SocialRESUMEN
Beside its hormonal function in salt and water homeostasis, vasopressin released into distinct brain areas plays a crucial role in stress-related behavior resulting in the enhancement of an anxious/depressive-like state. We aimed to investigate whether correction of the peripheral symptoms of congenital absence of AVP also corrects the behavioral alterations in AVP-deficient Brattleboro rats. Wild type (WT) and vasopressin-deficient (KO) male Brattleboro rats were tested. Half of the KO animals were treated by desmopressin (V2-receptor agonist) via osmotic minipump (subcutaneous) to eliminate the peripheral symptoms of vasopressin-deficiency. Anxiety was studied by elevated plus maze (EPM), defensive withdrawal (DW) and marble burying (MB) tests, while depressive-like changes were monitored in forced swimming (FS) and anhedonia by sucrose preference test. Cell activity was examined in septum and amygdala by c-Fos immunohistochemistry after 10 min FS. KO rats spent more time in the open arm of the EPM, spent less time at the periphery of DW and showed less burying behavior in MB suggesting a reduced anxiety state. KO animals showed less floating behavior during FS revealing a less depressive phenotype. Desmopressin treatment compensated the peripheral effects of vasopressin-deficiency without a significant influence on the behavior. The FS-induced c-Fos immunoreactivity in the medial amygdala was different in WT and KO rats, with almost identical levels in KO and desmopressin treated animals. There were no differences in central and basolateral amygdala as well as in lateral septum. Our data confirmed the role of vasopressin in the development of affective disorders through central mechanisms. The involvement of the medial amygdala in the behavioral alterations of vasopressin deficient animals deserves further attention.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Receptores de Vasopresinas/metabolismo , Tabique Pelúcido/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/metabolismo , Desamino Arginina Vasopresina/farmacología , Depresión/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Brattleboro , Tabique Pelúcido/metabolismo , Transducción de Señal/fisiología , NataciónRESUMEN
Opioids are among the world's oldest known drugs used mostly for pain relief, but recreational use is also widespread. A particularly important problem is opioid exposure in females, as their offspring can also be affected. Adverse intrauterine and postnatal environments can affect offspring development and may lead to various disabilities later in life. It is clear that repetitive painful experiences, such as randomly occurring invasive procedures during neonatal intensive care, can permanently alter neuronal and synaptic organization and therefore later behavior. At the same time, analgesic drugs can also be harmful, inducing neuronal apoptosis or withdrawal symptoms in the neonate and behavioral alterations in adulthood. Hence, risk-benefit ratios should be taken into consideration when pain relief is required during pregnancy or in neonates. Recreational use of opioids can also alter many aspects of life. Intrauterine opioid exposure has many toxic effects, inducing poor pregnancy outcomes due to underdevelopment, but it is believed that later negative consequences are more related to environmental factors such as a chaotic lifestyle and inadequate prenatal care. One of the crucial components is maternal care, which changes profoundly in addicted mothers. In substance-dependent mothers, pre- and postnatal care has special importance, and controlled treatment with a synthetic opioid (e.g., methadone) could be beneficial. We aimed to summarize and compare human and rodent data, as it is important to close the gap between scientific knowledge and societal policies. Special emphasis is given to gender differences in the sensitivity of offspring to perinatal opioid exposure.
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Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Femenino , Humanos , Drogas Ilícitas/efectos adversos , Recién Nacido , Masculino , Exposición Materna/efectos adversos , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos Mentales/inducido químicamente , Metadona/efectos adversos , Ratones , Morfina/efectos adversos , Dolor/tratamiento farmacológico , Embarazo , Ratas , Factores Sexuales , Estrés FisiológicoRESUMEN
The role of vasopressin in aggression received much attention in recent years. However, vasopressin has complex roles on social behavior, which are affected by social experience, motivation and hormonal background, suggesting that its effects depend on the condition of subjects. This hypothesis was tested here by studying the impact of vasopressin deficiency on aggressiveness in reproductively naive and reproductively experienced males, as well as in lactating females, with special reference to the patterns and contexts of attack behavior. We also studied effects on impulsiveness, a behavioral feature strongly related to aggression. Vasopressin deficiency did not affect aggressiveness in reproductively experienced males, decreased the share of violent attacks in reproductively inexperienced males without affecting total attack counts, and suppressed maternal aggression in both early and late phases of lactation; violent forms of attack were decreased in the latter but not the former phase. Changes in aggression appeared unrelated to general changes in maternal behaviors. Impulsivity in the delay discounting task was markedly decreased by vasopressin deficiency in lactating females but not males. Taken together, our findings confirm that vasopressin has an impact on aggressiveness, but show that this impact depends on the condition of subjects, and suggest that the effects of vasopressin on maternal aggression develop in conjunction with impulsivity. Interestingly, overall effects on aggression and specific effects on violent attacks dissociated in both males and females, which hints to the possibility that vasopressin has distinct roles in the development of escalated forms of aggression.
Asunto(s)
Agresión , Conducta Impulsiva , Vasopresinas/deficiencia , Vasopresinas/genética , Animales , Conducta Animal , Femenino , Lactancia/genética , Masculino , Conducta Materna , Ratas , Ratas Brattleboro , Ratas Transgénicas , Recompensa , Factores SexualesRESUMEN
Adaptation to stress is a basic phenomenon in mammalian life that is mandatorily associated with the activity of the hypothalamic-pituitary-adrenal (HPA) axis. An increased resting activity of the HPA axis can be measured during pregnancy and lactation, suggesting that these reproductive states lead to chronic load in females. In this study, we examined the consequences of the congenital lack of vasopressin on the activity of the HPA axis during lactation using vasopressin-deficient Brattleboro rats. Virgin and lactating, homozygous vasopressin-deficient rats were compared with control, heterozygous rats. In control dams compared with virgins, physiological changes similar to those observed in a chronic stress state (thymus involution, adrenal gland hyperplasia, elevation of proopiomelanocortin mRNA levels in the adenohypophysis, and resting plasma corticosterone levels) were observed. In vasopressin-deficient dams, adrenal gland hyperplasia and resting corticosterone level elevations were not observed. Corticotropin-releasing hormone (Crh) mRNA levels in the hypothalamic paraventricular nucleus were elevated in only the control dams, while oxytocin (OT) mRNA levels were higher in vasopressin-deficient virgins and lactation induced a further increase in both the genotypes. Suckling-induced ACTH and corticosterone level elevations were blunted in vasopressin-deficient dams. Anaphylactoid reaction (i.v. egg white) and insulin-induced hypoglycemia stimulated the HPA axis, which were blunted in lactating rats compared with the virgins and in vasopressin-deficient rats compared with the controls without interaction of the two factors. Vasopressin seems to contribute to the physiological changes observed during lactation mimicking a chronic stress state, but its role in acute HPA axis regulation during lactation seems to be similar to that observed in virgins. If vasopressin is congenitally absent, OT, but not the CRH, compensates for the missing vasopressin; however, the functional restitution remains incomplete.