Effects of the endogenous cannabimimetic anandamide were assessed over a wide dose range in a series of physiological and behavioral assays. These included the tetrad of tests in mice commonly used to assess cannabinoid-induced effects (motor activity, ring catalepsy, hypothermia, and analgesia tests), as well as a model for agonistic behavior on dyadic interactions of singly housed males with nonaggressive group-housed partners. Anandamide-induced effects on leukocyte phagocytosis were measured in a chemiluminescence assay. Results indicated that the higher doses tested (10-100 mg/kg) produced the well-known inhibitory effects in all of the above parameters as well as inhibition of phagocytosis. The lowest dose of anandamide tested (0.01 mg/kg) stimulated behavioral activities in the open field, on the ring and aggressive behavior in timid singly housed mice. This dose of 0.01 mg/kg, also stimulated phagocytosis. We suggest several possible mechanisms to explain these findings such as a differential involvement of a Gs and a Gi protein activated at low and high doses, respectively, allosteric modulation of the cannabinoid, and activation of presynaptic cannabinoid receptors by low doses of anandamide.

• MeSH
• agrese účinky léků   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• defekace účinky léků   MeSH
• endokanabinoidy MeSH
• fagocytóza účinky léků   MeSH
• inbrední kmeny myší MeSH
• kanabinoidy farmakologie   MeSH
• katalepsie chemicky indukované   MeSH
• kyseliny arachidonové farmakologie   MeSH
• leukocyty účinky léků   MeSH
• luminiscenční měření MeSH
• měření bolesti účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• polynenasycené alkamidy MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• anandamide MeSH Prohlížeč
• blokátory kalciových kanálů MeSH
• endokanabinoidy MeSH
• kanabinoidy MeSH
• kyseliny arachidonové MeSH
• polynenasycené alkamidy MeSH

Anandamide (AEA) is an important modulator of nociception in the spinal dorsal horn, acting presynaptically through Cannabinoid (CB1) and Transient receptor potential vanilloid (TRPV1) receptors. The role of AEA (1 µM, 10 µM, and 30 µM) application on the modulation of nociceptive synaptic transmission under control and inflammatory conditions was studied by recording miniature excitatory postsynaptic currents (mEPSCs) from neurons in spinal cord slices. Inhibition of the CB1 receptors by PF514273, TRPV1 by SB366791, and the fatty acid amide hydrolase (FAAH) by URB597 was used. Under naïve conditions, the AEA application did not affect the mEPSCs frequency (1.43±0.12 Hz) when all the recorded neurons were considered. The mEPSC frequency increased (180.0±39.2%) only when AEA (30 µM) was applied with PF514273 and URB597. Analysis showed that one sub-population of neurons had synaptic input inhibited (39.1% of neurons), the second excited (43.5%), whereas 8.7% showed a mixed effect and 8.7% did not respond to the AEA. With inflammation, the AEA effect was highly inhibitory (72.7%), while the excitation was negligible (9.1%), and 18.2% were not modulated. After inflammation, more neurons (45.0%) responded even to low AEA by mEPSC frequency increase with PF514273/URB597 present. AEA-induced dual (excitatory/inhibitory) effects at the 1st nociceptive synapse should be considered when developing analgesics targeting the endocannabinoid system. These findings contrast the clear inhibitory effects of the AEA precursor 20:4-NAPE application described previously and suggest that modulation of endogenous AEA production may be more favorable for analgesic treatments.

• Klíčová slova
• Anandamide, CB(1), FAAH, Spinal cord, Synaptic transmission, TRPV1,
• MeSH
• amidohydrolasy MeSH
• analgetika farmakologie   MeSH
• benzamidy * MeSH
• endokanabinoidy * farmakologie   MeSH
• karbamáty * MeSH
• kyseliny arachidonové * MeSH
• lidé MeSH
• nocicepce * MeSH
• polynenasycené alkamidy farmakologie   MeSH
• zadní rohy míšní MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amidohydrolasy MeSH
• analgetika MeSH
• anandamide MeSH Prohlížeč
• benzamidy * MeSH
• cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester MeSH Prohlížeč
• endokanabinoidy * MeSH
• karbamáty * MeSH
• kyseliny arachidonové * MeSH
• polynenasycené alkamidy MeSH

Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.

• MeSH
• endokanabinoidy * metabolismus   MeSH
• kationtové kanály TRPV metabolismus   MeSH
• kyseliny arachidonové * metabolismus   farmakologie   MeSH
• lidé MeSH
• mícha * metabolismus   účinky léků   MeSH
• nervový přenos * fyziologie   účinky léků   MeSH
• nocicepce fyziologie   účinky léků   MeSH
• nociceptory metabolismus   účinky léků   fyziologie   MeSH
• polynenasycené alkamidy * metabolismus   MeSH
• receptor kanabinoidní CB1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• anandamide MeSH Prohlížeč
• endokanabinoidy * MeSH
• kationtové kanály TRPV MeSH
• kyseliny arachidonové * MeSH
• polynenasycené alkamidy * MeSH
• receptor kanabinoidní CB1 MeSH

Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20:4-NAPE). We investigated the effect of the anandamide precursor 20:4-NAPE on synaptic activity in naive and inflammatory conditions. Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. Peripheral inflammation was induced by subcutaneous injection of carrageenan. Under naive conditions, mEPSCs frequency (0.96 ± 0.11 Hz) was significantly decreased after 20 μM 20:4-NAPE application (55.3 ± 7.4%). This 20:4-NAPE-induced inhibition was blocked by anandamide-synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. In addition, the inhibition was prevented by the CB1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor antagonist SB 366791 (10 μM). Under inflammatory conditions, 20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the TRPV1 receptor antagonist SB 366791 but not by PF 514273 application. Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. The switch between TRPV1 and CB1 receptor activation by the AEA precursor 20:4-NAPE during inflammation may play an important role in nociceptive processing, hence the development of pathological pain.

• Klíčová slova
• 20:4-NAPE, CB1, NAPE-PLD, TRPV1, anandamide, inflammation, spinal cord,
• Publikační typ
• časopisecké články MeSH

Cannabinoids exert various biological effects that are either receptor-mediated or independent of receptor signaling. Mitochondrial effects of cannabinoids were interpreted either as non-receptor-mediated alteration of mitochondrial membranes, or as indirect consequences of activation of plasma membrane type 1 cannabinoid receptors (CB1). Recently, CB1 receptors were confirmed to be localized to the membranes of neuronal mitochondria, where their activation directly regulates respiration and energy production. Here, we performed in-depth analysis of cannabinoid-induced changes of mitochondrial respiration using both an antagonist/inverse agonist of CB1 receptors, AM251 and the cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol (THC), cannabidiol, anandamide, and WIN 55,212-2. Relationships were determined between cannabinoid concentration and respiratory rate driven by substrates of complex I, II or IV in pig brain mitochondria. Either full or partial inhibition of respiratory rate was found for the tested drugs, with an IC50 in the micromolar range, which verified the significant role of non-receptor-mediated mechanism in inhibiting mitochondrial respiration. Effect of stepwise application of THC and AM251 evidenced protective role of AM251 and corroborated the participation of CB1 receptor activation in the inhibition of mitochondrial respiration. We proposed a model, which includes both receptor- and non-receptor-mediated mechanisms of cannabinoid action on mitochondrial respiration. This model explains both the inhibitory effect of cannabinoids and the protective effect of the CB1 receptor inverse agonist.

• Klíčová slova
• AM251, Anandamide, Cannabidiol, Respiratory rate, WIN 55,212-2, Δ(9)-Tetrahydrocannabinol,
• MeSH
• agonisté kanabinoidních receptorů farmakologie   MeSH
• benzoxaziny farmakologie   MeSH
• buněčné dýchání účinky léků   MeSH
• endokanabinoidy farmakologie   MeSH
• energetický metabolismus účinky léků   MeSH
• inverzní agonismus léků MeSH
• kanabidiol farmakologie   MeSH
• kanabinoidy farmakologie   MeSH
• kyseliny arachidonové farmakologie   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• morfoliny farmakologie   MeSH
• mozek účinky léků   metabolismus   MeSH
• naftaleny farmakologie   MeSH
• piperidiny farmakologie   MeSH
• polynenasycené alkamidy farmakologie   MeSH
• prasata MeSH
• pyrazoly farmakologie   MeSH
• receptor kanabinoidní CB1 účinky léků   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• tetrahydrokanabinol farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone MeSH Prohlížeč
• agonisté kanabinoidních receptorů MeSH
• AM 251 MeSH Prohlížeč
• anandamide MeSH Prohlížeč
• benzoxaziny MeSH
• endokanabinoidy MeSH
• kanabidiol MeSH
• kanabinoidy MeSH
• kyseliny arachidonové MeSH
• morfoliny MeSH
• naftaleny MeSH
• piperidiny MeSH
• polynenasycené alkamidy MeSH
• pyrazoly MeSH
• receptor kanabinoidní CB1 MeSH
• tetrahydrokanabinol MeSH

BACKGROUND: Human amniotic and amniochorionic membranes (AM, ACM) represent the most often used grafts accelerating wound healing. Palmitoylethanolamide, oleoylethanolamide and anandamide are endogenous bioactive lipid molecules, generally referred as N-acylethanolamines. They express analgesic, nociceptive, neuroprotective and anti-inflammatory properties. We assessed the distribution of these lipid mediators in placental tissues, as they could participate on analgesic and wound healing effect of AM/ACM grafts. METHODS: Seven placentas were collected after caesarean delivery and fresh samples of AM, ACM, placental disc, umbilical cord, umbilical serum and vernix caseosa, and decontaminated samples (antibiotic solution BASE 128) of AM and ACM have been prepared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used for N-acylethanolamines analysis. RESULTS: N-acylethanolamines were present in all studied tissues, palmitoylethanolamide being the most abundant and the anandamide the least. For palmitoylethanolamide the maximum average concentration was detected in AM (350.33 ± 239.26 ng/g), while oleoylethanolamide and anandamide were most abundant in placenta (219.08 ± 79.42 ng/g and 30.06 ± 7.77 ng/g, respectively). Low levels of N-acylethanolamines were found in serum and vernix. A significant increase in the levels of N-acylethanolamines (3.1-3.6-fold, P < 0.001) was observed in AM when the tissues were decontaminated using antibiotic solution. The increase in decontaminated ACM was not statistically significant. CONCLUSIONS: The presence of N-acylethanolamines, particularly palmitoylethanolamide in AM and ACM allows us to propose these lipid mediators as the likely factors responsible for the anti-hyperalgesic, but also anti-inflammatory and neuroprotective, effects of AM/ACM grafts in wound healing treatment. The increase of N-acylethanolamines levels in AM and ACM after tissue decontamination indicates that tissue processing is an important factor in maintaining the analgesic effect.

• MeSH
• analgetika MeSH
• endokanabinoidy * MeSH
• ethanolaminy MeSH
• lidé MeSH
• placenta * MeSH
• polynenasycené alkamidy MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• analgetika MeSH
• anandamide MeSH Prohlížeč
• endokanabinoidy * MeSH
• ethanolaminy MeSH
• N-acylethanolamines MeSH Prohlížeč
• oleoyl ethanolamine MeSH Prohlížeč
• palmidrol MeSH Prohlížeč
• polynenasycené alkamidy MeSH

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

• MeSH
• druhý trimestr těhotenství MeSH
• endokanabinoidy MeSH
• lidé MeSH
• novorozenec MeSH
• předčasný porod * diagnóza   MeSH
• samovolný potrat * MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anandamide MeSH Prohlížeč
• endokanabinoidy MeSH

RATIONALE AND OBJECTIVES: In addition to dopamine, endocannabinoids are thought to participate in neural reward mechanisms of opioids. Number of recent studies suggests crucial involvement of ghrelin in some addictive drugs effects. Our previous results showed that ghrelin participates in morphine-induced changes in the mesolimbic dopaminergic system associated with reward processing. The goal of the present study was to test whether the growth hormone secretagogue receptor (GHS-R1A) antagonist JMV2959 was able to influence morphine-induced effects on anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) in the nucleus accumbens shell (NACSh). METHODS: We used in vivo microdialysis to determine changes in levels of AEA and 2-AG in the NACSh in rats following (i) an acute morphine dose (5, 10 mg/kg s.c.) with and without JMV2959 pretreatment (3, 6 mg/kg i.p.) or (ii) a morphine challenge dose (5 mg/kg s.c.) with and without JMV2959 (3, 6 mg/kg i.p.) pretreatment, administered during abstinence following repeated doses of morphine (5 days, 10-40 mg/kg). Co-administration of ghrelin (40 ug/kg i.p.) was used to verify the ghrelin mechanisms involvement. RESULTS: Pretreatment with JMV2959 significantly and dose-dependently reversed morphine-induced anandamide increases in the NACSh in both the acute and longer-term models, resulting in a significant AEA decrease. JMV2959 significantly intensified acute morphine-induced decreases in accumbens 2-AG levels and attenuated morphine challenge-induced 2-AG decreases. JMV2959 pretreatment significantly reduced concurrent morphine challenge-induced behavioral sensitization. JMV2959 pretreatment effects were abolished by co-administration of ghrelin. CONCLUSIONS: Our results indicate significant involvement of ghrelin signaling in morphine-induced endocannabinoid changes in the NACSh.

• Klíčová slova
• 2-Arachidonoylglycerol, Acute, Anandamide, Challenge during abstinence, Endocannabinoids, Ghrelin, Microdialysis, Morphine, Neural reward system, Nucleus accumbens shell, Stereotyped behavior,
• MeSH
• endokanabinoidy metabolismus   fyziologie   MeSH
• extracelulární prostor účinky léků   metabolismus   MeSH
• ghrelin fyziologie   MeSH
• glyceridy metabolismus   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyseliny arachidonové metabolismus   MeSH
• morfin farmakologie   MeSH
• narkotika farmakologie   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• receptory somatotropinu antagonisté a inhibitory   MeSH
• stereotypní chování účinky léků   MeSH
• triazoly farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anandamide MeSH Prohlížeč
• endokanabinoidy MeSH
• ghrelin MeSH
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• glycin MeSH
• kyseliny arachidonové MeSH
• morfin MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• narkotika MeSH
• polynenasycené alkamidy MeSH
• receptory ghrelinu MeSH
• receptory somatotropinu MeSH
• triazoly MeSH

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2-induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

• Klíčová slova
• 2-arachidonoylglycerol/2-AG, GABA, addiction, anandamide/AEA, dopamine, dopamine metabolism, endocannabinoids, ghrelin/GHS-R1A, nucleus accumbens shell microdialysis, synthetic cannabinoid WIN55,212-2,
• MeSH
• benzoxaziny aplikace a dávkování   MeSH
• dopamin metabolismus   MeSH
• endokanabinoidy metabolismus   MeSH
• GABA metabolismus   MeSH
• ghrelin metabolismus   MeSH
• glyceridy metabolismus   MeSH
• glycin aplikace a dávkování   analogy a deriváty   MeSH
• kyseliny arachidonové metabolismus   MeSH
• morfoliny aplikace a dávkování   MeSH
• naftaleny aplikace a dávkování   MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• triazoly aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone MeSH Prohlížeč
• anandamide MeSH Prohlížeč
• benzoxaziny MeSH
• dopamin MeSH
• endokanabinoidy MeSH
• GABA MeSH
• ghrelin MeSH
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• glycin MeSH
• kyseliny arachidonové MeSH
• morfoliny MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• naftaleny MeSH
• polynenasycené alkamidy MeSH
• triazoly MeSH

In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.

• Klíčová slova
• FAAH, HPA-axis, N-Arachidonoylserotonin, Stress, TRPV1,
• MeSH
• amidohydrolasy antagonisté a inhibitory   genetika   metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• endokanabinoidy metabolismus   MeSH
• fyzické omezení MeSH
• glyceridy metabolismus   MeSH
• kationtové kanály TRPV antagonisté a inhibitory   genetika   metabolismus   MeSH
• kortikosteron krev   MeSH
• krysa rodu Rattus MeSH
• kyseliny arachidonové metabolismus   farmakologie   terapeutické užití   MeSH
• mozek účinky léků   metabolismus   MeSH
• mozkový neurotrofický faktor genetika   metabolismus   MeSH
• plavání MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• psychický stres krev   farmakoterapie   metabolismus   MeSH
• serotonin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• systém hypofýza - nadledviny MeSH
• systém hypotalamus-hypofýza MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amidohydrolasy MeSH
• anandamide MeSH Prohlížeč
• arachidonoylserotonin MeSH Prohlížeč
• endokanabinoidy MeSH
• fatty-acid amide hydrolase MeSH Prohlížeč
• glyceridy MeSH
• glyceryl 2-arachidonate MeSH Prohlížeč
• kationtové kanály TRPV MeSH
• kortikosteron MeSH
• kyseliny arachidonové MeSH
• mozkový neurotrofický faktor MeSH
• polynenasycené alkamidy MeSH
• serotonin MeSH
• Trpv1 protein, rat MeSH Prohlížeč