piperidines and staurosporine-aglycone

Pronociceptive responses to endothelins in the trigeminal system seem to be mediated by ET. ET-1 induced facial heat hyperalgesia that persisted up to 6h and was prevented by BQ-123, BQ-788 or by intraganglionar RTX injection. Likewise, local pre-treatment with BCTC abolished ET-1 induced facial heat hyperalgesia up to 3h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia.. In conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ET

Topics: Animals; Carbazoles; Diterpenes; Endothelin-1; Face; Female; Hot Temperature; Hyperalgesia; Indole Alkaloids; Nerve Growth Factor; Oligopeptides; Peptides, Cyclic; Piperidines; Pyrazines; Pyridines; Rats; Rats, Wistar; Trigeminal Ganglion

Brain-derived neurotrophic factor (BDNF) and endocannabinoids (eCBs) have been individually implicated in behavioral effects of cocaine. The present study examined how BDNF-eCB interaction regulates cocaine-induced synaptic plasticity in the ventral tegmental area and behavioral effects. We report that BDNF and selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF) activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic depression, depolarization-induced suppression of inhibition (DSI), and long-term depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse midbrain slices. The facilitation appears to be mediated by an increase in eCB production via phospholipase Cγ pathway, but not by an increase in CB1 receptor responsiveness or a decrease in eCB hydrolysis. Using Cre-loxP technology to specifically delete BDNF in dopamine neurons, we showed that eCB-mediated I-LTD, cocaine-induced reduction of GABAergic inhibition, and potentiation of glutamatergic excitation remained intact in wild-type control mice, but were impaired in BDNF conditional knock-out mice. We also showed that cocaine-induced conditioned place preference was attenuated in BDNF conditional knock-out mice, in vivo pretreatments with DHF before place conditioning restored cocaine conditioned place preference in these mice, and the behavioral effect of DHF was blocked by a CB₁ receptor antagonist. Together, these results suggest that BDNF in dopamine neurons regulates eCB responses, cocaine-induced synaptic plasticity, and associative learning.

Topics: Animals; Brain-Derived Neurotrophic Factor; Carbazoles; Cocaine; Conditioning, Operant; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Dopaminergic Neurons; Endocannabinoids; Enzyme Inhibitors; In Vitro Techniques; Indole Alkaloids; Mesencephalon; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuronal Plasticity; Piperidines; Pyrazoles; Receptors, Glutamate; RNA, Untranslated; Signal Transduction; Synapses; Time Factors

Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine.

Topics: Alkaloids; Animals; Antidepressive Agents; Benzodioxoles; Brain-Derived Neurotrophic Factor; Carbazoles; Chronic Disease; Disease Models, Animal; Enzyme Inhibitors; Food Preferences; Indole Alkaloids; Male; Mice; Mice, Inbred ICR; Piperidines; Polyunsaturated Alkamides; Signal Transduction; Stress, Psychological; Sucrose; Sweetening Agents; Time Factors

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raises the possibility that brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB may be important as modulators of this excitatory input into the SCN. To test this possibility, we used whole-cell patch-clamp methods to measure excitatory currents in rat SCN neurons. These currents were evoked by electrical stimulation of the optic nerve. We found that the amplitude of the N-methyl-D-aspartate (NMDA) component of the evoked excitatory postsynaptic currents (NMDA-EPSC) was increased by application of BDNF. The neurotrophin also increased the magnitude of NMDA-evoked currents in SCN neurons. The BDNF enhancement of the NMDA-EPSC was blocked by treatment with the neurotrophin receptor antagonist K252a as well as treatment with the soluble form of the TrkB receptor engineered as an immunoadhesin (TrkB IgG). Finally, the BDNF enhancement was lost in brain slices treated with the NR2B antagonist ifenprodil. The results demonstrate that BDNF and TrkB receptors are important regulators of retinal glutamatergic synaptic transmission within the SCN.

Topics: Animals; Brain-Derived Neurotrophic Factor; Carbazoles; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Immunoglobulin G; In Vitro Techniques; Indole Alkaloids; Male; Membrane Potentials; N-Methylaspartate; Neurons; Optic Nerve; Patch-Clamp Techniques; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, trkB; Receptors, N-Methyl-D-Aspartate; Suprachiasmatic Nucleus