RESUMEN
Beta-endorphin (ß-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how ß-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of ß-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.
Asunto(s)
Conducta/fisiología , Sistema Nervioso Central/fisiología , betaendorfina/fisiología , Animales , Conducta Animal/fisiología , Comunicación Celular , Ingestión de Alimentos , Espacio Extracelular/fisiología , Humanos , Motivación/fisiología , Dolor/fisiopatología , Recompensa , Conducta Sexual/fisiologíaRESUMEN
This review focuses on the role of serotonin and especially 5-HT1A receptors in female rat sexual behavior. In addition, the differences and/or similarities with male rats are discussed. Overall, in both males and females 5-HT1A receptors do not appear to be involved in sexual behavior under normal circumstances, but become very important under conditions of elevated serotonin levels. 5-HT1A receptor agonists facilitate sexual behavior in male rats, but inhibit female sexual activity. At first sight, this seems quite conflicting, but could be due to our definitions of different elements of sexual behavior. Three different phases can be distinguished in rats' sexual cycle, the introductory (precopulatory), the copulatory and the executive (ejaculatory) phases. Different mechanisms and brain regions are involved in these phases. If the appropriate phases of males and females are properly compared, the role of 5-HT1A receptors in rats might be more similar than assumed thus far.
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Receptor de Serotonina 5-HT1A/fisiología , Conducta Sexual Animal/fisiología , Animales , Monoaminas Biogénicas/fisiología , Encéfalo/anatomía & histología , Encéfalo/fisiología , Copulación/fisiología , Femenino , Masculino , Postura/fisiología , Ratas , Serotonina/fisiología , Caracteres SexualesRESUMEN
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling.
Asunto(s)
Antidepresivos/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Conducta Sexual Animal/efectos de los fármacos , Animales , Compuestos Aza/efectos adversos , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Bupropión/efectos adversos , Buspirona/efectos adversos , Ciclohexanoles/efectos adversos , Modelos Animales de Enfermedad , Dopamina/fisiología , Femenino , Humanos , Indoles/efectos adversos , Masculino , Norepinefrina/fisiología , Paroxetina/efectos adversos , Piridinas/efectos adversos , Ratas , Ratas Wistar , Serotonina/fisiología , Conducta Sexual Animal/fisiología , Disfunciones Sexuales Fisiológicas/inducido químicamente , Disfunciones Sexuales Fisiológicas/fisiopatología , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Clorhidrato de VenlafaxinaRESUMEN
Serotonin plays an important role in male sexual behavior. Many studies have been performed on the pivotal role of 5-HT1A receptors in sexual behavior. Overall, 5-HT1A receptors do not appear to be involved under normal circumstances, but become very important under conditions of elevated serotonin levels in sexual behavior. 5-HT1A receptor agonists facilitate ejaculatory behavior in male rats, while inhibiting copulatory behavior. Three different phases can be distinguished in rats' sexual cycle, the introductory (precopulatory), the copulatory and the executive (ejaculatory) phases. Different mechanisms and brain regions are involved in these phases. The mechanisms, brain regions and the possible involvement of 5-HT and 5-HT1A receptors in the appropriate phases in male rat sexual behavior will be discussed in the current review.
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Receptor de Serotonina 5-HT1A/fisiología , Conducta Sexual Animal/fisiología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Monoaminas Biogénicas/fisiología , Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Copulación/efectos de los fármacos , Copulación/fisiología , Eyaculación/efectos de los fármacos , Eyaculación/fisiología , Femenino , Masculino , Modelos Neurológicos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Ratas , Serotonina/fisiología , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Conducta Sexual Animal/efectos de los fármacosRESUMEN
The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways' from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology. Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral 'prosocial' effects: from social relations and 'trust' to treatment of 'autism'. Only very recently in a microdialysis study in rats and mice, the 'direct-nose-brain-pathways' of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the 'intrinsic' OT-system in the hypothalamus as well needs further clarification. We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects.
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Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Neuronas/efectos de los fármacos , Oxitocina/administración & dosificación , Conducta Social , Administración Intranasal , Animales , Humanos , Ratones , RatasRESUMEN
What can be learned from historical anatomical drawings and how to incorporate these drawings into anatomical teaching? The drawing "A skull sectioned" (RL 19058v) by Leonardo da Vinci (1452-1519), hides more detailed information than reported earlier. A well-chosen section cut explores sectioned paranasal sinuses and ductus nasolacrimalis. A dissected lateral wall of the maxilla is also present. Furthermore, at the level of the foramen mentale, the drawing displays compact and spongious bony components, together with a cross-section through the foramen mentale and its connection with the canalis mandibulae. Leonardo was the first to describe a correct dental formula (6424) and made efforts to place this formula above the related dental elements. However, taking into account, the morphological features of the individual elements of the maxilla, it can be suggested that Leonardo sketched a "peculiar dental element" on the position of the right maxillary premolar in the dental sketch. The fact that the author did not make any comment on that special element is remarkable. Leonardo could have had sufficient knowledge of the precise morphology of maxillary and mandibular premolars, since the author depicted these elements in the dissected skull. The fact that the author also had access to premolars in situ corroborates our suggestion that "something went wrong" in this part of the drawing. The present study shows that historical anatomical drawings are very useful for interactive learning of detailed anatomy for students in medicine and dentistry.
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Anatomía/historia , Cráneo/anatomía & histología , Diente/anatomía & histología , Historia del Siglo XV , Historia del Siglo XVI , ItaliaRESUMEN
Brain microvasculature plays a critical role in the regulation of homeostasis of neural tissues. The present study focuses on characteristic microvascular basement membrane (bm) aberrations in the midbrain periaqueductal gray matter (PAG) and their relation to aging. The PAG can be considered a caudal extension of the limbic system and is a key structure in the regulation of a myriad of autonomic and motor control functions. In an ultrastructural study, morphologic changes in mesencephalic PAG capillaries were assessed in aged and young hamster and compared with those in caudal brainstem areas. Bm aberrations were studied in 1200 capillaries (n = 600 young hamsters; n = 600 aged hamsters). A new, never reported variant of bm degeneration was found that presented itself as foamy-like structures accumulating within the lamina densa of notably PAG capillaries. We classified these foamy structures as 'spumiform basement membrane degenerations' (sbmd) in which we could distinguish 4 stages depending on the size and intramembranous localization, ranging from split bm (stage I), intermediate stages II and III, to extensive stage IV, affecting almost the complete capillary bm outline. In the PAG of senescent animals various stages of sbmd were observed in 92 ± 3% of all capillaries. Stage II was most prominently present (59%), followed by stage III (20%), and stage IV (13%). These bm aberrations were clearly age-dependent because in young animals, only 5% of the PAG capillaries showed characteristics of sbmd. For comparison, in the pontine reticular formation at the PAG-level, 41% of the capillaries showed a form of sbmd, but these defects were significantly less severe (stages I-II, 98%), and caudal brainstem structures displayed no sbmd at all. In addition to sbmd, diffuse endothelial changes, disrupted tight junctions, thickening of the bm, pericyte degeneration, and gliosis were observed in PAG capillaries. It is hypothesized that selective bm permeability of PAG capillaries results in a sequence of bm damage events that start with split bm, gradually changing into more and more extensive sbmd accumulations that eventually almost completely surround the capillary. Progressive sbmd in PAG capillaries might lead to a loss of blood-brain barrier function and consequently to impairment of autonomic and motor control functions exerted by the PAG.
Asunto(s)
Membrana Basal/ultraestructura , Tronco Encefálico/irrigación sanguínea , Tronco Encefálico/ultraestructura , Capilares/ultraestructura , Trastornos Cerebrovasculares/patología , Animales , Cricetinae , Femenino , MesocricetusRESUMEN
There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ß-endorphin (ß-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ß-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ß-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ß-END, independence of peripheral versus central levels, central ß-END migration over considerable distances, behavioral effects of ß-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.
RESUMEN
UNLABELLED: The nucleus pararetroambiguus (NPRA) and the commissural nucleus of the solitary tract (NTScom) show estrogen nuclear receptor-α immunoreactivity (nuclear ER-α-IR). Both cell groups are involved in estrous cycle related adaptations. We examined in normally cycling aged hamsters the occurrence/amount/frequency of age-related degenerative changes in NPRA and NTScom during estrus and diestrus. In 2640 electron microscopy photomicrographs plasticity reflected in the ratio of axon terminal surface/dendrite surface (t/d) was morphometrically analyzed. Medial tegmental field (mtf, nuclear ER-α-IR poor), served as control. In aged animals, irrespective of nuclear ER-α-IR+ or nuclear ER-α-IR- related cell groups, extensive diffuse degenerative structural aberrations were observed. The hormonal state had a strong influence on t/d ratios in NPRA and NTScom, but not in mtf. In NPRA and NTScom, diestrous hamsters had significantly smaller t/d ratios (NPRA, 0.750 ± 0.050; NTScom, 0.900 ± 0.039) than the estrous hamsters (NPRA, 1.083 ± 0.075; NTScom, 1.204 ± 0.076). Aging affected axodendritic ratios only in mtf (p < 0.001). IN CONCLUSION: in the female hamster brain, estrous cycle-induced structural plasticity is preserved in NPRA and NTScom during aging despite the presence of diffuse age-related neurodegenerative changes.
Asunto(s)
Envejecimiento , Tronco Encefálico/citología , Estrógenos/metabolismo , Neuronas/metabolismo , Conducta Sexual Animal/fisiología , Factores de Edad , Animales , Tronco Encefálico/metabolismo , Cricetinae , Receptor alfa de Estrógeno/metabolismo , Ciclo Estral/metabolismo , Femenino , Masculino , Microscopía Electrónica de Transmisión , Neuronas/ultraestructura , Factores de TiempoRESUMEN
Lipofuscin accumulation is a characteristic feature of senescent postmitotic neuronal cells but estrogen may have protecting effects by inhibiting its formation. In the present ultrastructural study, lipofuscin accumulation was studied in 2 estrogen-α-receptive brainstem areas: nucleus pararetroambiguus (NPRA) and the commissural part of the solitary tract nucleus/A2 catecholaminergic group (NTScom/A2) and compared with the estrogen-insensitive medial tegmental field (mtf), in young (23 weeks) and aged (95 weeks) female hamsters. In the aged animals, extensive intracytoplasmic lipofuscin accumulation was observed. A total number of 6450 neurons were classified in 4 categories. Levels were significantly elevated in each of the brain areas studied. Lipofuscin accumulation was strongest in the mtf, less in NPRA, and remarkably less in the area of NTScom/A2. In conclusion, the observed differences in lipofuscin accumulation suggest: (1) considerable regional differences in the degree of neuronal vulnerability; and (2) a possible neuroprotective role for estrogen, because the degree of accumulation is inversely related to the density of the estrogen receptors, varying from nonreceptive (mtf) to NPRA and NTScom/A2 (most receptive).
Asunto(s)
Envejecimiento/metabolismo , Tronco Encefálico/metabolismo , Lipofuscina/metabolismo , Neuronas/metabolismo , Envejecimiento/fisiología , Animales , Tronco Encefálico/fisiología , Senescencia Celular/fisiología , Cricetinae , Gránulos Citoplasmáticos/metabolismo , Gránulos Citoplasmáticos/fisiología , Receptor alfa de Estrógeno/metabolismo , Femenino , Masculino , Mesocricetus , Neuronas/fisiologíaRESUMEN
Serotonin plays an important role in both male and female sexual behaviour. In general, reduction of 5-HT function facilitates, whereas enhancement inhibits sexual behaviour. Most fundamental research on the involvement of 5-HT in sex has been performed in rats. Selective serotonin reuptake inhibitors (SSRIs) have comparable effects on male and female sexual behaviour in rats; they inhibit it but only after chronic administration. Activation of the 5-HT(1A) receptor facilitates sexual behaviour in male rats but inhibits sexual behaviour in female rats, suggesting a differential role for 5-HT(1A) receptors in male and female rats. Research on sexual behaviour in rats with null mutations in the serotonin transporter (SERT) indicated also a differential role for 5-HT(1A) receptors in male and female sexual behaviour. Evidence exists that different pools of 5-HT(1A) receptors have differential roles in various parts of the cascade of sexual events occurring during sexual interactions. Roles for other 5-HT receptors are less well defined although 5-HT(1B), 5-HT(2A/B) and 5-HT(7) receptors seem to be involved. Identification of putative differential or comparable roles in female and male sexual activities requires more research.
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Serotonina/metabolismo , Diferenciación Sexual , Conducta Sexual Animal/fisiología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Modelos Animales , Ratas , Receptores de Serotonina/genética , Serotonina/farmacología , Serotoninérgicos/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Conducta Sexual Animal/efectos de los fármacos , Factores de TiempoRESUMEN
The cerebrospinal fluid (CSF) usually is considered as a protective 'nutrient and waste control' system for the brain. Recent findings suggest, however, that the composition of CSF is actively controlled and may play an influential role in the changes in brain activity, underlying different behavioral states. In the present review, we present an overview of available data concerning the release of oxytocin into the CSF, the location of the oxytocin-receptive brain areas and the behavioral effects of intracerebroventricular oxytocin. About 80% of the oxytocin-receptive areas are located close to the ventricular or subarachnoid CSF, including the hypothalamic 'Behavior Control Column' (L.W.Swanson, 2003). As a conclusion we suggest that 'CSF-oxytocin' contributes considerably to the non-synaptic communication processes involved in hypothalamic-, brainstem- and olfactory brain areas and behavioral states and that the flowing CSF is used as a 'broadcasting system' to send coordinated messages to a wide variety of nearby and distant brain areas.
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Conducta/fisiología , Encéfalo/metabolismo , Oxitocina/líquido cefalorraquídeo , Animales , Conducta/clasificación , Encéfalo/citología , Ingestión de Alimentos/fisiología , Humanos , Neuronas/metabolismo , Conducta Sexual/fisiología , Conducta SocialRESUMEN
Structural neuronal plasticity is present in the nucleus para-retroambiguus (NPRA) and the commissural nucleus of the solitary tract/A2 group (NTScom/A2) in female hamsters. Both brainstem nuclei play a role in estrous cycle related autonomic adaptations. We investigated how aging affects the capillary condition in these adaptive brainstem regions. Senescent female hamsters (+/-95 weeks) were tested weekly for their 4-day estrous cycle. Subsequently morphological changes of NPRA and NTScom/A2 were compared with those of young (+/-20 weeks) females in an ultrastructural study. The medial tegmental field served as control area. In 841 capillaries (n=319 capillaries, young females (N=3); n=522 capillaries, aged females (N=4)) vascular aberrations were classified into 3 categories: endothelial and tight junction, basement membrane and pericyte aberrations. In old animals, capillaries showed marked endothelial changes, disrupted tight junctions, and thickening and splitting of basement membranes. Aberrations were found in 40-60% of all capillaries. About 70% of the pericytes contained degenerative inclusions. Despite this generalized vascular degeneration, the reproductive cycle of female hamsters was unaffected by vascular senescence. Perivascular fibrosis as reported in aging rats was never observed, which suggests the existence of species differences.
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Envejecimiento/fisiología , Barrera Hematoencefálica/patología , Tronco Encefálico/irrigación sanguínea , Tronco Encefálico/patología , Células Endoteliales/patología , Receptor alfa de Estrógeno/fisiología , Microvasos/patología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Astrocitos/ultraestructura , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/ultraestructura , Tronco Encefálico/ultraestructura , Cricetinae , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Ciclo Estral/fisiología , Femenino , Fibrosis , Masculino , Mesocricetus , Microscopía Electrónica de Transmisión , Microvasos/metabolismo , Microvasos/ultraestructura , Núcleo Solitario/irrigación sanguínea , Núcleo Solitario/patología , Núcleo Solitario/ultraestructuraRESUMEN
BACKGROUND: In recent years the Netherlands has witnessed a steep increase in the number of bodies donated for medical research and training. To explore this upward trend and motives for donation, a survey was conducted among registered body donors in the database of the Department of Anatomy at the University Medical Center of Groningen (UMCG). METHODS: In November 2008, postal questionnaires were sent to 996 people enrolled at the UMCG body donor database. The present study focuses on motives for donation and social background characteristics of the body donors. FINDINGS: Registered donors responded quickly and the survey response rate was high (76%). The mean age of respondents was 69 years and the majority described themselves as Dutch (98%) and non-church affiliated (79%). One quarter (25%) of the respondents are/were health care professionals and 11% involved in education. Principal factor analysis revealed three dimensions underlying ten different motivations for body donation: a desire to be useful after death, a negative attitude towards funerals and expression of gratitude. Despite the current economic recession only 8% of respondents are prompted by money motives to bequeath their bodies. CONCLUSIONS: The majority of motives for body donation stem from the wish to be useful after death. However, the present survey suggests that body donation is more than an altruistic act; people are also motivated by personal benefit. Results of our survey contradict the notion that body donation stems from loneliness. Many donors have a supportive social network and meaningful social relationships. People moreover propagate body donation within their social networks.
Asunto(s)
Altruismo , Cuerpo Humano , Motivación , Donantes de Tejidos , Obtención de Tejidos y Órganos , Anatomía/métodos , Actitud Frente a la Muerte , Femenino , Hospitales Universitarios , Humanos , Masculino , Países Bajos , Selección de Paciente , Investigación , Encuestas y Cuestionarios , Obtención de Tejidos y Órganos/estadística & datos numéricosRESUMEN
The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states.
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BACKGROUND: The amygdala is involved in the coordination of stress but is also an important gatekeeper involved in the regulation of vigilance. The amygdala is structurally complex, consisting of several nuclei with specific functions in the affective response to environmental stimuli. There are indications that the medial amygdaloid nucleus may be a pivotal player in acute responses to emotional environmental stimuli. METHODS: The present study therefore aimed to study the effects of bilateral electrolytic lesions of the medial amygdala on unconditioned anxiety-related behavior as well as a sensorimotor gating parameter (prepulse inhibition, PPI) in rats. Anxiety-related behavior was assessed with the use of stress-induced hyperthermia (SIH), light-enhanced startle (LES) and open field behavior. RESULTS: Bilateral electrolytic lesions of the medial amygdala decreased the SIH response and anxiety-related open field behavior. In contrast, lesioned animals displayed augmented LES and disrupted PPI. No changes in basal locomotor activity, body temperature and acoustic startle were found between lesioned and sham animals. CONCLUSIONS: The present study suggests that the medial amygdala is an important player in response to acute environmental stimuli. Decreased unconditioned psychological stress responses were found, whereas LES was enhanced and sensorimotor processing was disrupted. However, considering the existing data on basolateral amygdala involvement in PPI and bed nucleus of the stria terminalis involvement in LES, local infusion studies into the MeA should be performed to further substantiate these findings.
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Amígdala del Cerebelo/fisiología , Filtrado Sensorial/fisiología , Estrés Fisiológico/fisiología , Estimulación Acústica/psicología , Amígdala del Cerebelo/anatomía & histología , Animales , Ansiedad/fisiopatología , Temperatura Corporal/fisiología , Conducta Exploratoria/fisiología , Fiebre/fisiopatología , Masculino , Actividad Motora/fisiología , Ratas , Ratas Wistar , Reflejo de Sobresalto/fisiologíaRESUMEN
BACKGROUND: Fos expression in the lumbar spinal cord, resulting from a noxious electrical stimulus at the hindpaw, is hypothesized to originate from three sources: direct sensory input of the noxious stimulus, local interactions in the spinal cord, and input of modulating signals from supraspinal regions. Our aim in this study was to discriminate among these sources by eliminating the supraspinal input. METHODS: Therefore, a spinal block was administered in male Wistar rats by administering a local anesthetic (bupivacaine) through an intrathecal catheter at the mid-thoracic level. This thoracic spinal block completely suppressed the noxious stimulation-induced withdrawal reflex that is normally elicited by electrical stimulus. Fos immunoreactivity (Fos-IR) was quantified in all laminae of the L4 segment of the spinal cord. RESULTS: Noxious stimulation resulted in a general and strong increase in Fos-IR in the ipsilateral dorsal horn, mainly in Laminae I, II, and V. Thoracic spinal block caused a remarkable increase in the amount of Fos-IR in Lamina V, but had no significant effect on the Fos-IR in Laminae I and II. CONCLUSIONS: The increase in Fos-IR in Lamina V may have resulted from the interruption of a pain-modulating descending mechanism from the brain. A known modulating descending mechanism is the serotonergic system, controlled by the periaqueductal gray. This system inhibits the neurons in the superficial laminae. Another nonserotonergic system originates in the anterior pretectal nucleus. The latter facilitates neurons in the superficial laminae, while neurons in Lamina V are inhibited. We conclude that both systems are probably involved in the observed effects of the peripheral noxious stimulation given in the present model.
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Extremidades/inervación , Bloqueo Nervioso/métodos , Dolor/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/metabolismo , Anestésicos Locales/administración & dosificación , Animales , Bupivacaína/administración & dosificación , Estimulación Eléctrica , Inyecciones Espinales , Vértebras Lumbares , Masculino , Inhibición Neural , Dolor/fisiopatología , Dolor/prevención & control , Ratas , Ratas Wistar , Reflejo Anormal , Médula Espinal/fisiopatología , Vértebras Torácicas , Regulación hacia ArribaRESUMEN
Recent findings have challenged the traditional view that the thalamus is the primary driving source of generalized spike-wave discharges (SWDs) characteristic for absence seizures, and indicate a leading role for the cortex instead. In light of this we investigated the effects of thalamic lesions on SWDs and sleep spindles in the WAG/Rij rat, a genetic model of absence epilepsy. EEG was recorded from neocortex and thalamus in freely moving rats, both before and after unilateral thalamic ibotenic acid lesions. Complete unilateral destruction of the reticular thalamic nucleus (RTN) combined with extensive destruction of the thalamocortical relay (TCR) nuclei, resulted in the bilateral abolishment of SWDs and ipsilateral abolishment of sleep spindles. A suppression of both types of thalamocortical oscillations was found when complete or extensive damage to the RTN was combined with minor to moderate damage to the TCR nuclei. Lesions that left the rostral pole of the RTN and part of the TCR nuclei intact, resulted in an ipsilateral suppression of sleep spindles, but a large increase of bilateral SWDs. These findings demonstrate that the thalamus in general and the RTN in particular are a prerequisite for both the typical bilateral 7-11 Hz SWDs and natural occurring sleep spindles in the WAG/Rij rat, but suggest that different intrathalamic subcircuits are involved in the two types of thalamocortical oscillations. Whereas the whole RTN appears to be critical for the generation of sleep spindles, the rostral pole of the RTN seems to be the most likely part that generates SWDs.
Asunto(s)
Potenciales de Acción/fisiología , Epilepsia Tipo Ausencia/genética , Epilepsia Tipo Ausencia/fisiopatología , Fases del Sueño/fisiología , Tálamo/lesiones , Potenciales de Acción/genética , Animales , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Electroencefalografía , Epilepsia Tipo Ausencia/patología , Lateralidad Funcional/fisiología , Masculino , Ratas , Fases del Sueño/genética , Análisis Espectral , Tálamo/patología , Tálamo/fisiopatologíaRESUMEN
BACKGROUND: Although our understanding of nociceptive processing during anesthesia has increased greatly over the last decade, many patients still experience hyperalgesia and acute pain postoperatively. The noxious-induced withdrawal reflex (NIWR) model is specifically designed and validated to quantitatively study the reaction on painful, multimodal stimuli in animals under anesthetic conditions. Since the anesthetic mechanisms differ between inhaled anesthetics and opioids, we evaluated the differential effects of isoflurane and fentanyl on c-fos expression at the lumbar level as a measure of nociceptive information transfer during general anesthesia. METHODS: The experimental setup consisted of a randomized block design with four experimental groups: two light (3/4) minimum alveolar concentration (MAC) isoflurane anesthesia groups (unstimulated/NIWR-stimulated) and two NIWR-stimulated surgical anesthesia groups (1(1/2) MAC isoflurane anesthesia and (3/4) MAC isoflurane anesthesia combined with fentanyl 400-600 microg x kg(-1) x h(-1)). After 2 h of intermittent electrical stimulation of the hind paw of the rat, the number of Fos immunoreactive (Fos-IR) neurons in the dorsal horn was measured quantitatively. RESULTS: The main suppressive effects on lumbar c-fos expression of isoflurane were observed in the superficial lamina II (P = 0.02), whereas fentanyl showed the strongest effects in lamina V (P = 0.05). CONCLUSIONS: This study demonstrates that the NIWR model combined with spinal Fos-immunoreactivity is a suitable and useful model for evaluating the differential effects of inhaled anesthetics and opioids on nociceptive information transfer during general anesthesia.
Asunto(s)
Fentanilo/uso terapéutico , Isoflurano/uso terapéutico , Dolor/fisiopatología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/fisiología , Analgésicos/uso terapéutico , Anestesia , Animales , Quimioterapia Combinada , Estimulación Eléctrica , Vértebras Lumbares , Masculino , Dolor/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Ratas , Ratas Wistar , Médula Espinal/efectos de los fármacosRESUMEN
Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and mating-induced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were observed in the reduced numbers of mounts and intromissions over time and an increased ejaculation frequency on day 1. The first post-ejaculatory interval, however, was lengthened, while other behavioral parameters were unaffected. Fos-immunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and locus coeruleus) was strongly reduced after chronic administration. After mating, induction of Fos-immunoreactivity was observed in well-known areas like medial preoptic nucleus and the posterodorsal medial amygdaloid area. Apomorphine, however, reduced mating-induced Fos-immunoreactivity in the nucleus accumbens shell and prevented its occurrence in its core area. This remarkable apomorphine effect was not observed in any other brain area. We conclude that the behavioral (pro-erectile) effects of apomorphine are consistent over time, and that the diminished accumbens-Fos-immunoreactivity and the elongated post-ejaculatory interval may reflect a decreased response to remote cues from the estrus female.