Post-Harvest Atmospheric Pressure and Composition Modify the Concentration and Bioaccessibility of α- and ß-Carotene in Carrots and Sweet Potatoes.

Provitamin A (proVA) carotenoid synthesis and degradation are strongly influenced by environmental factors, including during post-harvest storage. Hypobaric and hyperbaric storages increase the shelf-life of many crops, but their effects on proVA carotenoids are not known. Our aim was to investigate the effects of modifications of atmospheric pressure and composition on α- and ß-carotene concentration and bioaccessibility during the post-harvest storage of carrots and sweet potatoes. Vegetables were stored for 11-14 days at 20 °C in the dark in chambers with modified pressure and O2 concentrations. In carrots, α- and ß-carotene concentrations increased significantly during storage, but compared to the control, they were significantly lower in hyperbaria (-23 and -26%, respectively), whereas they did not differ significantly in hypoxia and hypobaria. In sweet potatoes, α- and ß-carotene concentrations decreased significantly during storage, but neither hypoxia, hypobaria nor hyperbaria led to any significant change compared to the control. There was a significant increase for carrot α- and ß-carotene bioaccessibility in hypobaria and hyperbaria, while there was a significant decrease for sweet potato ß-carotene bioaccessibility in hypobaria/hypoxia and normobaria/hypoxia (-45% and -65% vs. control, respectively). Atmospheric pressure and composition during the post-harvest storage of carrots and sweet potatoes modified the concentration and bioaccessibility of proVA carotenoids.

Blood Adenosine Increase During Apnea in Spearfishermen Reinforces the Efficiency of the Cardiovascular Component of the Diving Reflex.

The physiopathology consequences of hypoxia during breath-hold diving are a matter of debate. Adenosine (AD), an ATP derivative, is suspected to be implicated in the adaptive cardiovascular response to apnea, because of its vasodilating and bradycardic properties, two clinical manifestations observed during voluntary apnea. The aim of this study was to evaluate the adenosine response to apnea-induced hypoxia in trained spearfishermen (SFM) who are used to perform repetitive dives for 4-5 h. Twelve SFM (11 men and 1 woman, mean age 41 ± 3 years, apnea experience: 18 ± 9 years) and 10 control (CTL) subjects (age 44 ± 7 years) were enrolled in the study. Subjects were asked to main a dry static apnea and stopped it when they began the struggle phase (average duration: SFM 120 ± 78 s, CTL 78 ± 12 s). Capillary blood samples were collected at baseline and immediately after the apnea and analyzed for standard parameters and adenosine blood concentration ([AD]b). Heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressures were also recorded continuously during the apnea. During the apnea, an increase in SBP and DBP and a decrease in HR were observed in both SFM and CTL. At baseline, [AD]b was higher in SFM compared with CTL (1.05 ± 0.2 vs. 0.73 ± 0.11 µM, p < 0.01). [AD]b increased significantly at the end of the apnea in both groups, but the increase was significantly greater in SFM than in controls (+90.4 vs. +12%, p < 0.01). Importantly, in SFM, we also observed significant correlations between [AD]b and HR (R = -0.8, p = 0.02), SpO2 (R = -0.69, p = 0.01), SBP (R = -0.89, p = 0.02), and DBP (R = -0.68, p = 0.03). Such associations were absent in CTL. The adenosine release during apnea was associated with blood O2 saturation and cardiovascular parameters in trained divers but not in controls. These data therefore suggest that adenosine may play a major role in the adaptive cardiovascular response to apnea and could reflect the level of training.

Physiological stress markers during breath-hold diving and SCUBA diving.

This study investigated the sources of physiological stress in diving by comparing SCUBA dives (stressors: hydrostatic pressure, cold, and hyperoxia), apneic dives (hydrostatic pressure, cold, physical activity, hypoxia), and dry static apnea (hypoxia only). We hypothesized that despite the hypoxia induces by a long static apnea, it would be less stressful than SCUBA dive or apneic dives since the latter combined high pressure, physical activity, and cold exposure. Blood samples were collected from 12SCUBA and 12 apnea divers before and after dives. On a different occasion, samples were collected from the apneic group before and after a maximal static dry apnea. We measured changes in levels of the stress hormones cortisol and copeptin in each situation. To identify localized effects of the stress, we measured levels of the cardiac injury markers troponin (cTnI) and brain natriuretic peptide (BNP), the muscular stress markers myoglobin and lactate), and the hypoxemia marker ischemia-modified albumin (IMA). Copeptin, cortisol, and IMA levels increased for the apneic dive and the static dry apnea, whereas they decreased for the SCUBA dive. Troponin, BNP, and myoglobin levels increased for the apneic dive, but were unchanged for the SCUBA dive and the static dry apnea. We conclude that hypoxia induced by apnea is the dominant trigger for the release of stress hormones and cardiac injury markers, whereas cold or and hyperbaric exposures play a minor role. These results indicate that subjects should be screened carefully for pre-existing cardiac diseases before undertaking significant apneic maneuvers.

Dopamine, Neurochemical Processes, and Oxygen Toxicity at Pressure.

All mammals, including man, exposed to breathing gas mixtures at high pressures exhibit central nervous system disturbances, which differ according to the gas used. With the use of compressed air, the increased oxygen partial pressure induces hyperoxic disturbances that consist of epileptic seizures that occur, on average, after 30 min exposure to 2.8 ATA in man or to 5 ATA in rats. Increased oxygen partial pressure induces reactive oxygen species and reactive nitrogen species production that could be related to neurotransmitter changes reported for the preepileptic phase or at pressures that produce epileptic seizures. In rats, oxygen pressures lower than 5 ATA induce a decrease of dopamine release in the stratum that could be due to disturbances of neurotransmitter regulatory processes that are different from those implicated for hyperbaric oxygen-induced epileptic seizures. © 2016 American Physiological Society. Compr Physiol 6:1339-1344, 2016.

Neurochemistry of Pressure-Induced Nitrogen and Metabolically Inert Gas Narcosis in the Central Nervous System.

Gases that are not metabolized by the organism are thus chemically inactive under normal conditions. Such gases include the "noble gases" of the Periodic Table as well as hydrogen and nitrogen. At increasing pressure, nitrogen induces narcosis at 4 absolute atmospheres (ATAs) and more in humans and at 11 ATA and more in rats. Electrophysiological and neuropharmacological studies suggest that the striatum is a target of nitrogen narcosis. Glutamate and dopamine release from the striatum in rats are decreased by exposure to nitrogen at a pressure of 31 ATA (75% of the anesthetic threshold). Striatal dopamine levels decrease during exposure to compressed argon, an inert gas more narcotic than nitrogen, or to nitrous oxide, an anesthetic gas. Inversely, striatal dopamine levels increase during exposure to compressed helium, an inert gas with a very low narcotic potency. Exposure to nitrogen at high pressure does not change N-methyl-d-aspartate (NMDA) glutamate receptor activities in Substantia Nigra compacta and striatum but enhances gama amino butyric acidA (GABAA) receptor activities in Substantia Nigra compacta. The decrease in striatal dopamine levels in response to hyperbaric nitrogen exposure is suppressed by recurrent exposure to nitrogen narcosis, and dopamine levels increase after four or five exposures. This change, the lack of improvement of motor disturbances, the desensitization of GABAA receptors on dopamine cells during recurrent exposures and the long-lasting decrease of glutamate coupled with the higher sensitivity of NMDA receptors, suggest a nitrogen toxicity induced by repetitive exposures to narcosis. These differential changes in different neurotransmitter receptors would support the binding protein theory. © 2016 American Physiological Society. Compr Physiol 6:1579-1590, 2016.

Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers: A Randomized Study.

Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing.Seventeen healthy male volunteers (mean age 35 ±â€Š11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels.No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ±â€Š0.08 µM) and during head-up tilt test (0.33 ±â€Š0.09 µM) when compared with baseline (0.6 ±â€Š0.1 µM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ±â€Š0.1 µM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air.These results suggest that hyperoxia was able to increase blood pressure during head-up tilt test via a decrease in plasma adenosine concentration. Our results also suggest that adenosine receptor antagonists are worth trying in neurocardiogenic syncope.

Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat.

The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species.

Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

Short-term development of behavioral sensitization to amphetamine requires N-methyl-D-aspartate- and nicotinic-dependent mechanisms in the nucleus accumbens.

Repeated administration of psychostimulant drugs, such as amphetamine, induces an enhanced behavioral response to subsequent drug challenge. This behavioral sensitization is proposed to model the increased drug craving observed in human psychostimulant abusers. Current thinking is that the ventral tegmental area, but not the nucleus accumbens, plays a critical role in the development of behavioral sensitization. Here, we report that the concomitant blockade of glutamatergic and nicotinic ionotropic receptors in the core of the nucleus accumbens blocks the development of behavioral sensitization to amphetamine and further abolishes the increase in extracellular dopamine release induced by amphetamine in the nucleus accumbens. These findings demonstrate that the development of behavioral sensitization to amphetamine depends, in addition to the well-known role of the ventral tegmental area, on glutamatergic and nicotinic-dependent mechanisms in the core of the nucleus accumbens and further indicate that the dopaminergic mesolimbic pathway must be viewed as a single coordinated system of critical importance in the development of behavioral sensitization to psychostimulant drugs.

Appearance of gas collections after scuba diving death: a computed tomography study in a porcine model.

INTRODUCTION: Postmortem computed tomography can easily demonstrate gas collections after diving accidents. Thus, it is often used to support the diagnosis of air embolism secondary to barotrauma. However, many other phenomenons (putrefaction, resuscitation maneuvers, and postmortem tissue offgassing) can also cause postmortem gas effusions and lead to a wrong diagnosis of barotrauma. OBJECTIVES: The aim of this study is to determine topography and time of onset of postmortem gas collections respectively due to putrefaction, resuscitation maneuvers, and tissue offgassing. MATERIALS AND METHODS: A controlled experimental study was conducted on nine pigs. Three groups of three pigs were studied postmortem by CT from H0 to H24: one control group of nonresuscitated nondivers, one group of divers exposed premortem to an absolute maximal pressure of 5 b for 16 min followed by decompression procedures, and one group of nondivers resuscitated by manual ventilation and thoracic compression for 20 min. The study of intravascular gas was conducted using CT scan and correlated with the results of the autopsy. RESULTS: The CT scan reveals that, starting 3 h after death, a substantial amount of gas is observed in the venous and arterial systems in the group of divers. Arterial gas appears 24 h after death for the resuscitated group and is absent for the first 24 h for the control group. Concerning the putrefaction gas, this provokes intravenous and portal gas collections starting 6 h after death. Subcutaneous emphysema was observed in two of the three animals from the resuscitated group, corresponding to the thoracic compression areas. CONCLUSION: In fatal scuba diving accidents, offgassing appears early (starting from the first hour after death) in the venous system then spreads to the arterial system after about 3 h. The presence of intra-arterial gas is therefore not specific to barotrauma. To affirm a death by barotrauma followed by a gas embolism, a postmortem scanner should be conducted very early. Subcutaneous emphysema should not be mistaken as diagnostic criteria of barotrauma because it can be caused by the resuscitation maneuvers.

Mechanism of action of nitrogen pressure in controlling striatal dopamine level of freely moving rats is changed by recurrent exposures to nitrogen narcosis.

In rats, a single exposure to 3 MPa nitrogen induces change in motor processes, a sedative action and a decrease in dopamine release in the striatum. These changes due to a narcotic effect of nitrogen have been attributed to a decrease in glutamatergic control and the facilitation of GABAergic neurotransmission involving NMDA and GABA(A) receptors, respectively. After repeated exposure to nitrogen narcosis, a second exposure to 3 MPa increased dopamine levels suggesting a change in the control of the dopaminergic pathway. We investigated the role of the nigral NMDA and GABA(A) receptors in changes in the striatal dopamine levels. Dopamine-sensitive electrodes were implanted into the striatum under general anesthesia, together with a guide-cannula for drug injections into the SNc. Dopamine level was monitored by in vivo voltammetry. The effects of NMDA/GABA(A) receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) on dopamine levels were investigated. Rats were exposed to 3 MPa nitrogen before and after five daily exposures to 1 MPa. After these exposures to nitrogen narcosis, gabazine, NMDA and AP7 had no effect on the nitrogen-induced increase in dopamine levels. By contrast, muscimol strongly enhanced the increase in dopamine level induced by nitrogen. Our findings suggest that repeated nitrogen exposure disrupted NMDA receptor function and decreased GABAergic input by modifying GABA(A) receptor sensitivity. These findings demonstrated a change in the mechanism of action of nitrogen at pressure.

A closed-circuit rebreather for the characterization of denitrogenation.

BACKGROUND: The denitrogenation methods currently used to characterize the washout kinetics of body nitrogen require costly devices that are not easily transportable for measurements in real conditions. An original and simple system to measure the denitrogenation kinetics of the human body at rest and at ambient pressure is presented here. METHODS: The nitrogen content accumulated in the loop of a closed-circuit rebreather supplied by pure oxygen was determined using galvanic oxygen sensors and a small size data logger for pressure, temperature, and relative humidity measurements. The method was applied to three subjects through a preliminary validation phase. The collected data, after processing, were compared: 1) to the results found in previous papers for similar experiments using other methods; and 2) to the results of a physiological gas exchanges model. RESULTS: Denitrogenation curves for 60-min and 120-min durations were obtained for the three subjects, with an interindividual variability being in agreement with their body fat percentage (560 +/- 140 ml for the subject with less body fat and 880 +/- 70 ml for the subject with more body fat) after 60 min. Both the experimental results found in the literature and the simulation results were compared to the present results. CONCLUSION: From a preliminary analysis, the proposed denitrogenation procedure proved to be adequate compared to other methods. An investigation of the method demonstrated that the system accuracy can be improved. A validation phase using more subjects may support the use of this new technology.

A pressurized nitrogen counterbalance to cortical glutamatergic pathway stimulation.

Previous microdialysis studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by nitrogen narcosis. We sought to establish the hypothetical role of the glutamatergic corticostriatal pathway because of the glutamate deficiency which occurs in the basal ganglia in this hyperbaric syndrome. Retrodialysis with 1 mM of Saclofen and 100 mM of KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of glutamate by 95.2% and no changes in dopamine levels. Under 3 MPa of nitrogen and with the infusion, the rate of striatal glutamate decreased by 51.3%, to a greater extent than under pressurised nitrogen alone (-23.8%). The rate of dopamine decreased, which also occurred under pressurised nitrogen (-36.9 and -31.4%, respectively). In conclusion, the function of the corticostriatal pathway is affected by nitrogen under pressure. This suggests that the nitrogen-induced break point seems to be located at the glutamatergic striatopetal neurons.

How can an inert gas counterbalance a NMDA-induced glutamate release?

Previous neurochemical studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by inert gas narcosis. We sought to establish the hypothetical role of glutamate and its main receptor, the N-methyl-d-aspartate (NMDA) receptor, in this syndrome. We aimed to counteract the nitrogen narcosis-induced glutamate and dopamine decreases by stimulating the NMDA receptor in the striatum. We used bilateral retrodialysis on awake rats, submitted to nitrogen under pressure (3 MPa). Continuous infusion of 2 mM of NMDA under normobaric conditions (0.01 MPa) (n = 8) significantly increased extracellular average levels of glutamate, aspartate, glutamine, and asparagine by 241.8%, 292.5%, 108.3%, and 195.3%, respectively. The same infusion conducted under nitrogen at 3 MPa (n = 6) revealed significant lower levels of these amino acids (n = 8/6, P > 0.001). In opposition, the NMDA-induced effects on dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA) levels were statistically not affected by the nitrogen at 3 MPa exposure (n = 8/6, P > 0.05). Dopamine was increased by >240% on average. HVA was decreased (down to 40%), and there was no change in DOPAC levels, in both conditions. Results highlight that the NMDA receptor is not directly affected by nitrogen under pressure as indicated by the elevation in NMDA-induced dopamine release under hyperbaric nitrogen. On the other hand, the NMDA-evoked glutamate increase is counteracted by nitrogen narcosis. No improvement in motor and locomotor disturbances was observed with high striatal concentration in dopamine. Further experiments have to be done to specify why the striatal glutamate pathways, in association with the inhibition of its metabolism, only are affected by nitrogen narcosis in this study.

Low susceptibility to inert gases and pressure symptoms in TREK-1-deficient mice.

Nervous disorders may occur after an organism is saturated with inert gases, which may alter the lipid bilayer structure, according to their liposolubility coefficient. Increase in the nitrogen partial pressure induces a neurological syndrome called 'nitrogen narcosis'. By contrast, high pressures of helium induce epilepsy, an high-pressure nervous syndrome symptom. On the basis of an analogy with anaesthetic mechanisms, we used TREK-1 knockout mice, earlier described to volatile the anaesthetics resistance. These mice had a higher threshold of resistance to the narcotic effects of nitrogen and to the death after recurrent epileptic seizure induced by high pressure. TREK-1 channels seem to play a key role in modulating the anaesthetic potential of inert gases and in neuroprotection.

Repeated administration of amphetamine induces a shift of the prefrontal cortex and basolateral amygdala motor function.

The role of the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in the expression of behavioural locomotor sensitization to amphetamine (Amph) has been poorly studied. In the present study, we investigated how lidocaine infused in the mPFC or BLA modulated motor responses to acute and repeated (sensitization) Amph administration. We showed that reversible blockade of mPFC or BLA by lidocaine increased both locomotor and rearing responses to acute Amph, but blocked the expression of behavioural sensitization to Amph. These findings indicate that under free-lidocaine conditions repeated administration of Amph would produce a shift of mPFC and BLA motor function from an inhibitory to a facilitatory role in response to Amph. We propose that this phenomenon may be of major critical importance in the development of drug dependence.

Comparison of nitrogen narcosis and helium pressure effects on striatal amino acids: a microdialysis study in rats.

Exposure to nitrogen-oxygen mixture at high pressure induces narcosis, which can be considered as a first step toward general anaesthesia. Narcotic potencies of inert gases are attributed to their lipid solubility. Nitrogen narcosis induces cognitive and motor disturbances that occur from 0.3 MPa in man and from 1 MPa in rats. Neurochemical studies performed in rats up to 3 MPa have shown that nitrogen pressure decreases striatal dopamine release like argon, another inert gas, or nitrous oxide, an anaesthetic gas. Striatal dopamine release is under glutamatergic and other amino acid neurotransmission regulations. The aim of this work was to study the effects of nitrogen at 3 MPa on striatal amino acid levels and to compare to those of 3 MPa of helium which is not narcotic at this pressure, by using a new technique of microdialysis samples extraction under hyperbaric conditions, in freely moving rats. Amino acids were analysed by HPLC coupled to fluorimetric detection in order to appreciate glutamate, aspartate, glutamine and asparagine levels. Nitrogen-oxygen mixture exposure at 3 MPa decreased glutamate, glutamine and asparagine concentrations. In contrast, with helium-oxygen mixture, glutamate and aspartate levels were increased during the compression phase but not during the stay at maximal pressure. Comparison between nitrogen and helium highlighted the narcotic effects of nitrogen at pressure. As a matter of fact, nitrogen induces a reduction in glutamate and in other amino acids that could partly explain the decrease in striatal dopamine level as well as the motor and cognitive disturbances reported in nitrogen narcosis.

Alterations in nigral NMDA and GABAA receptor control of the striatal dopamine level after repetitive exposures to nitrogen narcosis.

Nitrogen pressure exposure in rats results in decreased dopamine (DA) release at the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, demonstrating the narcotic potency of nitrogen. This effect is attributed to decreased excitatory and increased inhibitory inputs to dopaminergic neurons, involving a change in NMDA and GABA(A) receptor function. We investigated whether repetitive exposures to nitrogen modify the excitatory and inhibitory control of the dopaminergic nigro-striatal pathway. We used voltammetry to measure dopamine levels in freely-moving rats, implanted with dopamine-sensitive electrodes in the striatum. NMDA/GABA(A) receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) were administered through a guide-cannula into the SNc, and their effects on striatal dopamine levels were measured under normobaric conditions, before and after five repetitive exposures to 1 MPa nitrogen. NMDA-mediated dopamine release was greater following repetitive exposures, AP7-mediated inhibition of glutamatergic input was blocked, suggesting that NMDA receptor sensitivity was increased and glutamate release reduced. Muscimol did not modify dopamine levels following repetitive exposures, whereas the effect of gabazine was greater after exposures than before. This suggested that interneuronal GABA(A) receptors were desensitized, leading to an increased GABAergic input at dopaminergic cells. Thus, repetitive nitrogen exposure induced persistent changes in glutamatergic and GABAergic control of dopaminergic neurons, resulting in decreased activity of the nigrostriatal pathway.

Modulation by the dorsal, but not the ventral, hippocampus of the expression of behavioural sensitization to amphetamine.

Although the dorsal hippocampus (DH) and the ventral hippocampus (VH) densely innervate the nucleus accumbens, which mediates the expression of behavioural sensitization, the respective and specific contribution of DH and VH in the expression of behavioural sensitization to amphetamine has not been investigated. In the present study, we investigated how lidocaine infused in DH or VH modulated behavioural locomotor sensitization induced by repeated administration of systemic amphetamine. Rats, well habituated to their environmental conditions and experimental protocol, were given repeated administration of systemic amphetamine. Once behavioural sensitization was developed, rats were challenged with amphetamine and infused with saline (controls) or lidocaine into DH or VH. We found that reversible inhibition by lidocaine of DH, but not VH, blocks the expression of behavioural sensitization to amphetamine. Control animals injected with saline solution do express behavioural sensitization. Our results bring new insights on the role of the hippocampus complex in the expression of behavioural sensitization, indicating that, in individuals well habituated to the drug-associated context, DH but not VH would play a key role. The results provide experimental evidence for clinical studies in human addicts that have demonstrated that exposure to environmental stimuli associated with drug-taking behaviour elicits craving and can promote relapse, and further suggest that in drug abusers, once addiction has occurred, the contextual and spatial conditions that are associated with drug consumption may play a critical role in the maintenance of drug abuse.

The role of NMDA and GABAA receptors in the inhibiting effect of 3 MPa nitrogen on striatal dopamine level.

Nitrogen pressure exposure, in rats, resulted in a decreased dopamine (DA) level by the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, due to the narcotic potency of nitrogen. In the SNc, the nigrostriatal pathway is under glutamatergic and GABAergic control mediated by ion-channel NMDA and GABA(A) receptors, main targets of volatile anesthetics. The aim of this study was to investigate the role of these receptors in the regulation of striatal dopamine level under nitrogen narcosis. Under general anesthesia, male Sprague-Dawley rats were bilaterally implanted in the striatum with dopamine-sensitive electrodes and, in the SNc, with guide cannulae for drug injections. After recovery from surgery, the striatal dopamine level was quantified using differential pulse voltammetric measurements in freely moving rats. Focal injections of agonists (NMDA/muscimol) and antagonists (AP7/gabazine) of NMDA/GABA(A) receptors were made within SNc. Both normobaric condition and 3 MPa nitrogen pressure were studied. Control experiments confirmed a direct glutamatergic control on the striatal DA level through NMDA receptors. Both direct and indirect GABAergic control through two different types of GABA(A) receptors located on GABAergic interneurons and on DA cells were indicated. Under nitrogen pressure, the decrease in dopamine level (20%) was suppressed by both NMDA and GABA(A) agonist infusion. There was an unexpected increasing DA level, induced by AP7 (about 10%) and gabazine (about 30%). These results indicate that NMDA receptors remain functional and suggest a decreased glutamate release. The findings also describe an increase of GABA(A) receptor-mediated inhibition on DA cells under nitrogen pressure exposure.