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Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and neuropathic pain may be partially mediated by(More)
Adenosine levels increase at seizure foci as part of a postulated endogenous negative feedback mechanism that controls seizure activity through activation of A1 adenosine receptors. Agents that amplify this site- and event-specific surge of adenosine could provide antiseizure activity similar to that of adenosine receptor agonists but with fewer(More)
Recent evidence suggests that spinal cord glia can contribute to enhanced nociceptive responses. However, the signals that cause glial activation are unknown. Fractalkine (CX3C ligand-1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents. In the dorsal spinal cord, fractalkine receptors are(More)
Indiplon (NBI 34060; N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-alpha]pyrimidin-7-yl]phenyl]acetamide), a novel pyrazolopyrimidine and high-affinity allosteric potentiator of GABA(A) receptor function, was profiled for its effects in rodents after oral administration. In mice, indiplon inhibited locomotor activity (ED(50) = 2.7 mg/kg p.o.) at doses(More)
Although there is considerable information regarding the role of brain CRF in energy balance, relatively little is known about the role of urocortin (UCN), which is an equally potent anorexic agent. Therefore, the effects of intracerebroventricular (icv) administration of UCN (0.01-1 nmol/day) on food intake and body weight were assessed over a period of 13(More)
Corticotropin-releasing factor (CRF) is one of the principle components of the stress response. The physiological effects of CRF are mediated by two receptor subtypes, CRF(1) and CRF(2). Recent data obtained with the selective CRF(2) antagonist antisauvagine-30 (ASV-30) has begun to suggest that both CRF receptor subtypes may play a role in stress-related(More)
We compared the in vivo efficacy of two selective CRF2 agonists, mouse urocortin II (mUcn II) and human urocortin III (hUcn III), using food intake, anxious behavior, or ACTH release in CD-1 or Balb/c mice as indices of biological stress responses. All three peptides produced anorexia (Minimal Effective Dose (M.E.D.) for CRF and mUcn II = 0.03 nmol; M.E.D.(More)
Glutamate- and GABA-releasing neurons form the basis for neurotransmission in the mammalian central nervous system (CNS). The co-ordination of these excitatory and inhibitory systems, together with intrinsic voltage-gated ion channels and G-protein-coupled receptor modulation, provides the diverse neuronal firing patterns, network activity and synaptic(More)
In this study, we describe the pharmacological characterization of novel aryl-ether, biaryl, and fluorene aspartic acid and diaminopropionic acid analogs as potent inhibitors of EAAT2, the predominant glutamate transporter in forebrain regions. The rank order of potency determined for the inhibition of human EAAT2 was(More)
The adenosine kinase inhibitor, 5'-deoxyiodotubercidin (5dITU), was examined in a rat focal stoke model with temporary (105 min) middle cerebral artery occlusion (MCAO) followed by a 24 h recovery period. Inhibition of this adenosine metabolizing enzyme indirectly enhances the actions of endogenous adenosine without inducing cardiovascular side effects.(More)