Preventative and therapeutic effects of a GABA transporter 1 inhibitor administered systemically in a mouse model of paclitaxel-induced neuropathic pain.

Background: There is a dearth of drugs to manage a dose-limiting painful peripheral neuropathy induced by paclitaxel in some patients during the treatment of cancer. Gamma-aminobutyric acid transporter-1 (GAT-1) whose expression is increased in the brain and spinal cord during paclitaxel-induced neuropathic pain (PINP) might be a potential therapeutic target for managing PINP. Thus, our aim was to evaluate if systemic administration of a GAT-1 inhibitor ameliorates PINP.

Coadministration of indomethacin and minocycline attenuates established paclitaxel-induced neuropathic thermal hyperalgesia: Involvement of cannabinoid CB1 receptors.

Taxanes such as paclitaxel, which are chemotherapeutic drugs, cause dose-dependent painful neuropathy in some patients. We investigated whether coadministration of minocycline and indomethacin produces antinociceptive effects in mice with paclitaxel-induced neuropathic thermal hyperalgesia and if the cannabinoid system is involved. Previously, we reported that coadministration of these two drugs results in antinociception against inflammatory pain at doses where either drug alone lack significant activity.

Gait analysis of C57BL/6 mice with complete Freund's adjuvant-induced arthritis using the CatWalk system.

Background: The CatWalk system, a video based automated gait analysis system developed to evaluate footfall and gait changes in rodents, has been used for studying rodent models of arthritis, mainly the rat model. However, it has not been used to study static and dynamic gait parameters in mice with complete Freund's adjuvant (CFA). CFA is used extensively to induce arthritis in rodents including mice.

Matrix metalloproteinase inhibitor COL-3 prevents the development of paclitaxel-induced hyperalgesia in mice.

Objective: To study the potential of chemically modified tetracycline-3 (COL-3), a potent matrix metalloproteinase (MMP) inhibitor, to protect against the development of paclitaxel-induced painful neuropathy and its immunomodulatory effects.

Materials And Methods: The reaction latency to thermal stimuli (hot plate test) of female BALB/c mice was recorded before and after treatment with paclitaxel (2 mg/kg i.p.

Assessment of weight bearing changes and pharmacological antinociception in mice with LPS-induced monoarthritis using the Catwalk gait analysis system.

Aims: We evaluated the possibility of using the video-based Catwalk gait analysis method to measure weight bearing changes and for testing pharmacological antinociception in freely moving mice with lipopolysaccharide (LPS)-induced monoarthritis.

Main Methods: LPS or its solvent (PBS) was injected intra-articularly into the right hind (RH) limb ankle joint through the Achilles tendon of C57BL/6 mice. The Catwalk system was used to assess behavioral changes in freely moving mice.

Cholecystokinin-2 receptors couple to cAMP-protein kinase A to depress excitatory synaptic currents in rat nucleus accumbens in vitro.

We recently reported that the activation of cholecystokinin-2 receptors depress evoked excitatory postsynaptic currents (EPSCs) in nucleus accumbens (NAc) indirectly through gamma-aminobutyric acid (GABA) acting on gamma-aminobutyric acid-B (GABA(B)) receptors. Here, we determined the second messenger system that couples cholecystokinin-2 receptors to the observed synaptic depression. Using in vitro forebrain slices of rats and whole-cell patch recording, we tested the hypothesis that cholecystokinin-2 receptors are coupled to cAMP and protein kinase A signaling pathway.

Cholecystokinin inhibits evoked inhibitory postsynaptic currents in the rat nucleus accumbens indirectly through gamma-aminobutyric acid and gamma-aminobutyric acid type B receptors.

We recently reported that cholecystokinin (CCK) excited nucleus accumbens (NAc) cells and depressed excitatory synaptic transmission indirectly through gamma-aminobutyric acid (GABA), acting on presynaptic GABAB receptors (Kombian et al. [2004] J. Physiol.

Cholecystokinin activates CCKB receptors to excite cells and depress EPSCs in the rat rostral nucleus accumbens in vitro.

The peptide cholecystokinin (CCK) is abundant in the rat nucleus accumbens (NAc). Although it is colocalized with dopamine (DA) in afferent terminals in this region, neurochemical and behavioural reports are equally divided as to whether CCK enhances or diminishes DA's actions in this nucleus. To better understand the role of this peptide in the physiology of the NAc, we examined the effects of CCK on excitatory synaptic transmission and tested whether these are dependent on DA and/or other neuromodulators.

Dopamine and adenosine mediate substance P-induced depression of evoked IPSCs in the rat nucleus accumbens in vitro.

The major projection cells of the nucleus accumbens (NAc) are under a strong inhibitory influence from GABAergic afferents and depend on afferent excitation to produce their output. We have earlier reported that substance P (SP), a peptide which is colocalized with GABA in these neurons, depresses excitatory synaptic transmission in this nucleus (Kombian, S.B.

Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms.

Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized.