h is capable of dispersing cells from established biofilms, is one of the most frequently suggested strategies for the treatment for staphylococcal infections. However, as indicated by the data presented here, the use of matrix-degrading enzymes or other compounds leading to biofilm disassembly need to be carefully considered as biofilm-released cells can heighten the inflammatory response of the 
host consequently augmenting disease severity. ~~ Moreover, preliminary analysis suggested that Gpr139 knockout mice display deficits in locomotion, balance and sensorimotor tasks. The expression pattern of GPR139 and the initial phenotypic analysis of the lossof-function are consistent with a role in the modification of locomotor activity. Recently, while this study was in progress, it was found that GPR139 agonists reduce locomotor activity in rats. Variations in the Gpr139 locus have been linked to inattention in ADHD patients and to schizophrenia. Parkinson’s disease is the second-most prevalent neurodegenerative disease. The etiology of PD is still unknown in most cases, but the characteristic motor symptoms of PD are primarily due to the loss of neurons of the nigrostriatal dopaminergic pathway. Treatment of PD at present is symptomatic, induces side effects and does not stop disease progression. There is thus a huge need for innovative and new treatment strategies. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine is converted into the active 1-methyl-4-phenylpyridinium ion in the brain and can produce similar biochemical and neuropathological defects as observed in PD patients. These include the progressive loss of DA neurons in the substantia nigra pars compacta and the decrease of striatal dopamine levels. Therefore, it is one of the most widely used experimental models for sporadic PD. Lipophilic MPTP passes the blood-brain barrier and cellular membranes. In astrocytes, monoamine oxidase B converts MPTP into MPP+. MPP+ is taken up into DA neurons by the dopamine transporter inhibiting mitochondrial complex I. It promotes ATP depletion and generation of reactive oxygen species, which can activate apoptotic pathways. Rotenone is another mitochondrial complex 1 inhibitor applied in PD models, but unlike MPP+ it is lipophilic and can therefore readily cross the cell membranes. 6-Hydroxydopamine is taken up both by the DAT and the noradrenergic transporter, and therefore induces cell death in both DA and noradrenergic neurons. Like MPP+ and rotenone 6-OHDA is used for both in vitro and in vivo models for investigations of the underlying mechanism of PD. Recently, three agonists and an antagonist were developed as tools to further examine GPR139 function, one of which has been described. Here, we examined whether GPR139 signaling could modify toxicity of those most commonly used toxins used in PD models. We assessed toxin resistance of PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19815860 primary DA cells pre-treated with the GPR139 agonists, and whether protection by GPR139 signaling could be blocked by Rutin site coincubation with the antagonist. MATERIALS AND METHODS Compounds Compound 1 The GPR139 agonist compound 1, 2-N–hydrazinecarboxamide, with an EC50 of 39 nM has been described earlier. EC50 and IC50 for all compounds were determined as described. NMR and MS for the Preparation of Compound 2 and 3 The 1 H NMR spectra were recorded on a Bruker Avance AV with tetramethylsilane as internal standard. ESI-MS spectra were measured with a Thermo Finnigan LCQ14ECAXP or a PE-Sciex API 1SO-E
