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PubMed2005

The role of the cannabinoid system in nicotine addiction.

Nicotine, the main psychoactive component in tobacco smoke, appears to play a major role in tobacco addiction, producing a high morbidity and mortality in the world. A great amount of research has been developed to elucidate the neural pathways and neurotransmitter systems involved in such a complex addictive behaviour. One possible candidate is the cannabinoid system, which has been reported to participate in the addictive properties of other drugs of abuse. This review is focused on the recent pharmacological and molecular studies assessing cannabinoid-nicotine interactions, with special attention to those studies evaluating the behavioural responses related to the development of nicotine addiction.

Animals↗

PubMed2005

Limb preference in children with obstetric brachial plexus palsy.

Brachial plexus palsy affects children differently than adults. In children with obstetric brachial plexus palsy, motor development must depend on nervous system adaptation. Previous studies report sensory plasticity in these children. This noninvasive study provides support for neural plasticity (the general ability of the brain to reorganize neural pathways based on new experiences) in children with obstetric brachial plexus palsy by considering upper limb preference. As in the general population, we expect that 90% of children would prefer their right upper limb. However, only 17% of children affected by right obstetric brachial plexus palsy prefer the right upper limb for overall movement; children with left obstetric brachial plexus palsy did not significantly differ from the general population in upper limb preference. This study also provides the first evidence of a significant correlation between actual task performance and select obstetric brachial plexus palsy outcome measurement systems, thereby justifying the routine use of these outcome measurement systems as a reflection of the practical utility of the affected limb to the patient.

Birth Injuries↗

PubMed2007

Motilin activates neurons in the rat amygdala and increases gastric motility.

Motilin and motilin receptors have been found in most regions of the brain, including the amygdala, one of the most important parts of the limbic system. Our previous study found that administration of motilin in the hippocampus stimulates gastric motility. We now explore the effect of motilin in the amygdala on gastric motility. In conscious rats, gastric motility was recorded after microinjection of motilin, motilin receptor antagonist (GM-109) or a mixture of the two into the basomedial amygdala nucleus (BMA). In anesthetized rats the changes of spontaneous discharges of gastric distention sensitive neurons (GDSN) in the BMA were recorded after intracerebroventricular (i.c.v.) microinjection of motilin or GM-109. In conscious rats the amplitude of gastric contractions increased dose-dependently after microinjection of motilin in the BMA, and decreased after microinjection of GM-109. The excitatory or inhibitory effects induced by motilin or GM-109 alone, were weakened by microinjection of a mixture solution of both. The spontaneous discharge frequency of gastric distention excitatory neuron (GDEN) was mainly inhibited by i.c.v. microinjection of motilin but excited by GM-109. In contrast, the spontaneous discharge frequency of gastric distention inhibitory neuron (GDIN) was mainly excited by motilin, but inhibited by GM-109. Our findings suggest that motilin may regulate gastric motility by modulating neural pathways in the BMA.

Amygdala↗

PubMed2005

Purinergic P2 receptors as targets for novel analgesics.

Following hints in the early literature about adenosine 5'-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves. Since then, there has been an increasing number of papers exploring the role of P2X3 homomultimer and P2X2/3 heteromultimer receptors on sensory nerves in a wide range of organs, including skin, tongue, tooth pulp, intestine, bladder, and ureter that mediate the initiation of pain. Purinergic mechanosensory transduction has been proposed for visceral pain, where ATP released from epithelial cells lining the bladder, ureter, and intestine during distension acts on P2X3 and P2X2/3, and possibly P2Y, receptors on subepithelial sensory nerve fibers to send messages to the pain centers in the brain as well as initiating local reflexes. P1, P2X, and P2Y receptors also appear to be involved in nociceptive neural pathways in the spinal cord. P2X4 receptors on spinal microglia have been implicated in allodynia. The involvement of purinergic signaling in long-term neuropathic pain and inflammation as well as acute pain is discussed as well as the development of P2 receptor antagonists as novel analgesics.

Analgesics↗

PubMed2004

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain.

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Delta(9)-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 microg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.

Animals↗

PubMed2004

The anxiogenic video-recorded Stroop Color-Word Test: psychological and physiological alterations and effects of diazepam.

From among the few human experimental models that can be used to predict the clinical activity of new anxiolytic drugs, the video-recorded Stroop Color-Word Test (VRSCWT), which uses subjective scales to evaluate anxious states, is notable for its simplicity. However, considering that the choice of treatment for anxiety disorders is heavily dependent on the level of somatic symptomatology, a quantitative evaluation of the physiological alterations elicited by the anxiogenic situation of the VRSCWT would also be of great interest. In the present study, 36 healthy male and female volunteers were submitted to either the VRSCWT or to a nonanxiogenic test. The results showed that, as well as a sensation of anxiety, the VRSCWT elicited increases in heart rate and gastrocnemius tension. Subsequently, a further 48 healthy men and women were randomly assigned to three treatments: placebo, 5 and 10 mg of diazepam, and were submitted to the VRSCWT. The results showed that in men, diazepam blocked the feeling of anxiety elicited by the test, although it did not prevent the physiological alterations, while in women, there was no response to the anxiolytic action of the drug. Taken as a whole, these results suggest that the VRSCWT is an efficient method of inducing anxiety experimentally. It is able to elicit observable psychological and physiological alterations and can detect the blocking, by an anxiolytic, of the feelings of anxiety in healthy men. Furthermore, the results suggest that the neural pathways for the control of the psychological and physiological manifestations of anxiety may be separate. This study also draws attention to the fact that gender is an important variable in the evaluation of anxiolytic drugs.

Adolescent↗

PubMed2005

Environmental enrichment alters plus maze, but not maternal defense performance in mice.

Maternal defense behavior (or maternal aggression) is a highly conserved behavior for protecting offspring that is normally associated with decreased fear and anxiety in rodent dams. Environmental enrichment can decrease indices of fearfulness and anxiety (and elevate novelty seeking) in laboratory animals. This study examined whether enrichment could alter levels of maternal aggression and elevated plus maze performance in lactating mice. One group of female mice was exposed to a series of novel objects for 1.5 months while the other group was not. As expected, mice that had been exposed to an enriched environment showed significantly more entries to and time on the open arms of an elevated plus maze while they were lactating. Enriched mice showed similar maze performances when tested 3 months later in a non-lactating state, even though enrichment had been removed for 3 months. Further, offspring of enriched dams exhibited maze performance similar to that of their dams, suggesting possible epigenetic influences on maze performance. In contrast, no differences in measures of maternal aggression or pup retrieval were detected between enriched and control lactating mice. Together, these results indicate that environmental enrichment has long lasting effects on plus maze performance, but does not alter maternal aggression. The findings also suggest that whatever neural pathways are altered by enrichment do not strongly overlap or regulate those governing maternal aggression.

Aggression↗

PubMed2006

Thermoregulatory behavior is disrupted in rats with lesions of the anteroventral third ventricular area (AV3V).

Core body temperature is maintained through a combination of physiological and behavioral effector mechanisms. While the neural pathways involved in autonomic responses to a heat stress are slowly being unraveled, those controlling behavioral responses have remained elusive. We have recently demonstrated that the tissue that surrounds the anteroventral third ventricular region (AV3V) has an important role in the autonomic response to a heat stress. The purpose of the present study was to determine the impact lesions of the AV3V have on naturally occurring thermoregulatory behaviors. Core temperature was elevated at a constant rate (0.03 degrees C/min) for 90 min using an infrared heat lamp. Animals were videotaped and scored throughout the heating protocol for grooming, escape jumps and postural extension. The frequency of escape jumps and adoption of an extended posture were significantly reduced in AV3V-lesion rats. In contrast, grooming behavior was unaffected by AV3V lesions, although heat-induced salivation was markedly attenuated. These results demonstrate that the AV3V region is pivotal in the regulation of both autonomic and behavioral thermoregulatory effector mechanisms.

Animals↗

PubMed2004

Mechanisms of chronic cough.

Chronic and uncontrollable cough is one of the most common and debilitating symptoms found in patients with chronic airway diseases. The physical trauma and stresses of chronic cough on the airway mucosa and respiratory muscles can further worsen the deteriorating process of the airway diseases. The articles presented in this section focus primarily on the effect of chronic cough on the cell structure and protective function of the airway mucosa, the mechanisms underlying the hypersensitivity of chronic cough, and new target areas for antitussive drug development. A major emphasis has been placed on the neuronal plasticity found at the peripheral and central sites of the neural pathway mediating the cough reflex, and its potential role in the development of chronic cough is discussed. A number of new and important questions concerning the physiological and pharmacological mechanisms underlying chronic cough have emerged in these presentations. Further studies are required to answer these questions, which should bring a better understanding of the pathogenic mechanisms of chronic cough and lead to the development of new therapeutic strategies.

Antitussive Agents↗

PubMed2004

Sensory regulation of the cough reflex.

Coughing is a highly coordinated reflex that serves to protect the airways from a variety of potentially harmful stimuli. However, in airways disease the cough reflex threshold is lowered and coughing can become exaggerated and inappropriate. Excessive coughing not only affects an individual's quality of life, but may contribute to the pathology of the disease. Understanding the neural components of the cough reflex is essential for establishing new treatments for cough disorders. This review will summarize the current understanding of the afferent neural pathways mediating cough, including how interactions between airway afferent nerve fibre subtypes may modulate the cough reflex pathway and underlie the manifestation of cough disorders.

Animals↗

PubMed2004

Anorexigenic effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide in the chick brain are mediated by corticotrophin-releasing factor.

Intracerebroventricular (ICV) injection of pituitary adenylate cyclase-activating polypeptide-38 (PACAP) or vasoactive intestinal peptide (VIP) inhibits feeding in chicks. However, the underlying anorexigenic mechanism(s) has not yet been investigated. The present study investigated whether these peptides influence the activity of corticotrophin-releasing factor (CRF) neural pathways in the brain of chicks. Firstly, we found that ICV injections of PACAP and VIP increased plasma corticosterone concentrations. The corticosterone-releasing effect of PACAP was completely attenuated by co-injection of astressin, a CRF receptor antagonist, but this effect was only partial for VIP. These results demonstrated that CRF neurons mediate the actions of PACAP and, to a lesser extent, VIP, and suggest that the signaling mechanisms differ between the two peptides. This difference may arise from the two peptides interacting with different receptors because the corticosterone-releasing effect of PACAP, but not VIP, was completely attenuated by co-injection of PACAP (6-38), a PACAP receptor antagonist. Finally, we examined the effect of ICV co-injection of astressin on the anorexigenic effects of PACAP and VIP and found that the effects of both peptides were attenuated by astressin. Overall, the present study suggests that the anorexigenic effects of PACAP and VIP are mediated by the activation of CRF neurons.

Animals↗

PubMed2005

Altered cardiovascular responses to chronic angiotensin II infusion in aged rats.

In this work we determined by telemetry the cardiovascular effects produced by Ang II infusion on blood pressure (BP) and heart rate (HR) in aged rats. Male Wistar aged (48-52 weeks) and young (12 weeks) rats were used. Ang II (6 microg/h, young, n=6; aged, n=6) or vehicle (0.9% NaCl 1 microl/h, young, n=4; aged, n=5) were infused subcutaneously for 7 days, using osmotic mini-pump. The basal diurnal and nocturnal BP values were higher in aged rats (day: 98+/-0.3 mm Hg, night: 104+/-0.4 mm Hg) than in the young rats (day: 92+/-0.2 mm Hg, night: 99+/-0.2 mm Hg). In contrast, the basal diurnal and nocturnal HR values were significantly smaller in the aged rats. Ang II infusion produced a greater increase in the diurnal BP in the aged rats (Delta MAP=37+/-1.8 mm Hg) compared to the young ones (Delta MAP=30+/-3.5 mm Hg). In contrast, the nocturnal MAP increase was similar in both groups (young rats; Delta MAP=22+/-3.0 mm Hg, aged rats; Delta MAP=24+/-2.6 mm Hg). During Ang II infusion HR decreased transiently in the young rats. An opposite trend was observed in the aged rats. Ang II infusion also inverted the BP circadian rhythm, in both groups. No changes in HR circadian rhythm were observed. These differences suggest that the aging process alters in a different way Ang II-sensitive neural pathways involved in the control of autonomic activity.

Aging↗

PubMed2005

Developmental plasticity of the hypoxic ventilatory response after perinatal hyperoxia and hypoxia.

Both genetic and environmental factors influence the normal development of the respiratory control system. This review examines the role perinatal O2 plays in the development of normoxic breathing and the hypoxic ventilatory response in mammals. Hyperoxia and hypoxia elicit plasticity in respiratory control that is unique to development and may persist weeks to years after return to normoxia. Specifically, both hyperoxia and hypoxia during early postnatal development attenuate the adult hypoxic ventilatory response, but the underlying mechanisms for this plasticity differ. Hyperoxia attenuates the hypoxic ventilatory response through potentially life-long changes in carotid body function. Neonatal hypoxia appears to have short-term effects on carotid body function, but persistent changes in the hypoxic ventilatory response may instead reflect changes in respiratory mechanics or related neural pathways. Overall, it appears that a relatively narrow range of environmental O2 is consistent with "normal" postnatal respiratory control development, predisposing animals to potentially maladaptive plasticity in the face of disease or atypical environmental conditions.

Animals↗

PubMed2004

Induction of audiogenic seizures in imipenem/cilastatin-treated rats.

We investigated the effect of intense audiogenic stimulation (AGS) on rats treated with the antibiotic imipenem and dipeptidase inhibitor cilastatin (Imi/Cil). Under pentobarbital anesthesia (40 mg/kg) adult male Wistar rats were implanted with electrodes and cannulas were placed in the right lateral ventricle. Animals were divided into the following groups: (1) vehicle, (2) Imi/Cil 10 microg/10 microg, (3) Imi/Cil 25 microg/25 microg, (4) vehicle+AGS, (5) Imi/Cil 10 microg/10 microg +AGS, and (6) Imi/Cil 25 microg/25 microg +AGS. Imi/Cil was administered intracerebroventricularly in 5 microl of physiological saline. AGS (100+/-3 dB, 60 seconds) was applied at 15-minute intervals after the injection. Imi/Cil-induced seizures (twitching, forelimb clonus, headnodding, rearing, and clonic convulsions) and Imi/Cil-audio-induced seizures (wild running, clonic and tonic convulsions) were scored according to appropriate rating scales. Imi/Cil provoked convulsions dose-dependently. Each behavioral seizure response had a characteristic EEG correlate. AGS by itself did not provoke seizures in untreated rats. Sound stimulation in Imi/Cil-injected rats elicited typical audiogenic seizures, which were induced during five AGS tests (75 minutes postinjection). In most cases audiogenic seizures were not associated with epileptiform activity in the EEG, indicating that spreading of seizures did not involve the cortex. Since Imi/Cil-induced and Imi/Cil-audio-induced seizures differed behaviorally and electroencephalographically, it is suggested that different neural pathways are responsible for these two types of seizures: neuronal networks in the cortex are involved in Imi/Cil-induced seizures, whereas audiogenic seizures use networks residing primarily in the brainstem.

Animals↗

PubMed2003

Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness.

Appropriate regulatory control of the hypothalamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting 'reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such 'anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, 'anticipatory' circuits are integrated with neural pathways subserving 'reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary-adrenocortical dysfunction associated with numerous disease processes.

Adrenocorticotropic Hormone↗

PubMed2005

Time keeping by the quail's eye: circadian regulation of melatonin production.

Previous studies have shown that eye removal disrupts the circadian body temperature and activity rhythms of Japanese quail supporting the hypothesis that the eyes act as pacemakers within the quail circadian system. Furthermore, the putative ocular pacemakers are coupled to the rest of the circadian system via neural and hormonal outputs. Although the neural pathway has yet to be identified, experiments suggest that the daily rhythm of ocular melatonin synthesis and release is the hormonal output. We sought to strengthen the hypothesis that the eyes are the loci of circadian pacemakers, and that melatonin output is involved, by examining melatonin secretion in cultured quail retinas. Using an in vitro flow-through system we demonstrated that (1) isolated retinal tissue could exhibit a rhythm of melatonin release, (2) the rhythm of melatonin synthesis is directly entrainable by 24-h light-dark cycles, and (3) supplementation of the culture medium with serotonin is necessary for robust, rhythmic production of melatonin in constant darkness. These results show definitively that the eyes are the loci of a biological clock and, in light of previous studies showing the disruptive effects of blinding on the circadian system, strengthen the hypothesis that the ocular clock is a circadian pacemaker that can affect the rest of the circadian system via the cyclic synthesis and release of melatonin. The quail retina is proving to be a valuable in vitro model for investigating properties of circadian pacemakers.

5-Hydroxytryptophan↗

PubMed2004

The nose knows who's who: chemosensory individuality and mate recognition in mice.

Individual recognition is an important component of behaviors, such as mate choice and maternal bonding that are vital for reproductive success. This article highlights recent developments in our understanding of the chemosensory cues and the neural pathways involved in individuality discrimination in rodents. There appear to be several types of chemosensory signal of individuality that are influenced by the highly polymorphic families of major histocompatibility complex (MHC) proteins or major urinary proteins (MUPs). Both have the capability of binding small molecules and may influence the individual profile of these chemosignals in biological fluids such as urine, skin secretions, or saliva. Moreover, these proteins, or peptides associated with them, can be taken up into the vomeronasal organ (VNO) where they can potentially interact directly with the vomeronasal receptors. This is particularly interesting given the expression of major histocompatibility complex Ib proteins by the V2R class of vomeronasal receptor and the highly selective responses of accessory olfactory bulb (AOB) mitral cells to strain identity. These findings are consistent with the role of the vomeronasal system in mediating individual discrimination that allows mate recognition in the context of the pregnancy block effect. This is hypothesized to involve a selective increase in the inhibitory control of mitral cells in the accessory olfactory bulb at the first level of processing of the vomeronasal stimulus.

Animals↗

PubMedDate not supplied

[Central projections of the rat recurrent laryngeal nerve].

Laryngeal nerves contain the fibres that control the laryngeal function. The studies carried out on the rat with the purpose of having a better knowledge of the functional components and the real origin of the fibres conveyed by the recurrent laryngeal nerve (RLN) are few and in disagreement. No one of such papers were developed using biotinylated dextrane amines (BDA), a powerful tool for tracing neural pathways. The aim of our study was to identify in the rat using BDA, the nuclei of real origin of the fibres of the RLN, knowing in this way the functional components of this nerve. The study has been developed in 31 adult male Sprague-Dawley rats, applying the BDA into the lesioned RLN. The results obtained in all the animals show that the rat's RLN does not contain afferent fibres, whereas the efferent fibres were originated within the ipsilateral nucleus ambiguus (NA). So, in the rat, the RLN seems to contain exclusively efferent fibres, probably been the superior laryngeal nerve who conveyed the afferent fibres.

Animals↗