Neuroscience
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ATP, via activation of P2X3 receptors, has been highlighted as a key target in inflammatory hyperalgesia. Therefore, the aim of this study was to confirm whether the activation of P2X3 receptors in the gastrocnemius muscle of rats induces mechanical muscle hyperalgesia and, if so, to analyze the involvement of the classical inflammatory mediators (bradykinin, prostaglandins, sympathetic amines, pro-inflammatory cytokines and neutrophil migration) in this response. Intramuscular administration of the non-selective P2X3 receptor agonist α,β-meATP in the gastrocnemius muscle of rats induced mechanical muscle hyperalgesia, which, in turn, was prevented by the selective P2X3 and P2X2/3 receptors antagonist A-317491, the selective bradykinin B1-receptor antagonist Des-Arg9-[Leu8]-BK (DALBK), the cyclooxygenase inhibitor indomethacin, the β1- or β2-adrenoceptor antagonist atenolol and ICI 118,551, respectively. ⋯ Together, these findings suggest that α,β-meATP induced mechanical hyperalgesia in the gastrocnemius muscle of rats via activation of peripheral P2X3 receptors, which involves bradykinin, prostaglandins, sympathetic amines, pro-inflammatory cytokines release and neutrophil migration. It is also indicated that bradykinin is the key modulator of the mechanical muscle hyperalgesia induced by P2X3 receptors. Therefore, we suggest that P2X3 receptors are important targets to control muscle inflammatory pain.
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Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. ⋯ Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus of adolescent and adult mice.
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Gap junctions provide for direct intercellular electrical and metabolic coupling. The abundance of gap junctions at "large myelinated club ending (LMCE)" synapses on Mauthner cells (M-cells) of the teleost brain provided a convenient model to correlate anatomical and physiological properties of electrical synapses. There, presynaptic action potentials were found to evoke short-latency electrical "pre-potentials" immediately preceding their accompanying glutamate-induced depolarizations, making these the first unambiguously identified "mixed" (i.e., chemical plus electrical) synapses in the vertebrate CNS. ⋯ The widespread distribution of heterotypic gap junctions at glutamatergic mixed synapses throughout goldfish brain and spinal cord implies that pre- vs. postsynaptic asymmetry at electrical synapses evolved early in the chordate lineage. We propose that the advantages of the molecular and functional asymmetry of connexins at electrical synapses that are so prominently expressed in the teleost CNS are unlikely to have been abandoned in higher vertebrates. However, to create asymmetric coupling in mammals, where most gap junctions are composed of connexin36 (Cx36) on both sides, would require some other mechanism, such as differential phosphorylation of connexins on opposite sides of the same gap junction or on asymmetric differences in the complement of their scaffolding and regulatory proteins.
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The transition from sleep to the awake state is regulated by the activation of subcortical nuclei of the brainstem (BS) and basal forebrain (BF), releasing acetylcholine and glutamate throughout the cortex and inducing a tonic state of neural activity. It has been suggested that such activation is also mediated by the massive and diffuse cortical release of nitric oxide (NO). In this work we have combined the spectroscopic measurement of NO levels in the somatosensory cortex of the cat through its marker methemoglobin, as well as two other hemodynamic markers (oxyhemoglobin--oxyHb--and deoxyhemoglobin--deoxyHb), together with the electrical stimulation of BS and BF--to induce an experimental transition from a sleep-like state to an awake-like mode. ⋯ The changes induced by BF were monophasic lasting for up to 20s. The systemic blockade of NO production abolished the observed responses to BS whereas responses to BF stimulation were much less affected. These results indicate a crucial role for NO in the neuronal activation induced by the ascending systems.
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In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmaline-induced amnesia were examined in male mice. A one-trial step-down passive avoidance task was used for the assessment of memory retention in adult male mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1 mg/kg) induced impairment of memory retention. ⋯ However, pre-training intra-CA1 injection of SKF38393 (0.1 μg/mouse) or quinpirole (0.1 μg/mouse) increased pre-training harmaline (0.25 and 0.5 mg/kg, i.p.)-induced retrieval impairment. Moreover, SKF Ca blocker (SKF) (0.01 μg/mouse) decrease the amnesia induced by harmaline (1 mg/kg), while co-administration of SKF (0.01 μg/mouse)/sulpiride (0.25 μg/mouse) or SCH23390 (0.001 μg/mouse)/sulpiride (0.25 μg/mouse) potentiate amnesia caused by harmaline. These findings implicate the involvement of CA1 dopaminergic mechanism in harmaline-induced impairment of memory acquisition.