The police response to homelessness

This reports covers recommendations for best practices in police engagement with homeless people

Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacological strategies reduces acute alcohol-induced sedation and motor impairment in mice

Background and purposeEmerging evidence implicates a role for toll-like receptor 4 (TLR4) in the CNS effects of alcohol. The aim of the current study was to determine whether TLR4-MyD88-dependent signalling is involved in the acute behavioural actions of alcohol and if alcohol can activate TLR4-downstream MAPK and NF-κB pathways.Experimental approachThe TLR4 pathway was evaluated using the TLR4 antagonist (+)-naloxone (µ-opioid receptor-inactive isomer) and mice with null mutations in the TLR4 and MyD88 genes. Sedation and motor impairment induced by a single dose of alcohol were assessed by loss of righting reflex (LORR) and rotarod tests, separately. The phosphorylation of JNK, ERK and p38, and levels of IκBα were measured to determine the effects of acute alcohol exposure on MAPK and NF-κB signalling.Key resultsAfter a single dose of alcohol, both pharmacological inhibition of TLR4 signalling with (+)-naloxone and genetic deficiency of TLR4 or MyD88 significantly (P Conclusions and implicationsThese data provide new evidence that TLR4-MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.Yue Wu, Erin L Lousberg, Lachlan M Moldenhauer, John D Hayball, Janet K Coller, Kenner C Rice, Linda R Watkins, Andrew A Somogyi and Mark R Hutchinso