“
“Earlier studies suggest that opioid receptors in the ventral tegmental area, but not the nucleus accumbens (NAc), play a role in relapse to drug-seeking behavior. However, environmental stimuli that elicit relapse also release

the endogenous opioid beta-endorphin in the NAc. Using a within-session extinction/reinstatement paradigm in rats that self-administer cocaine, we found that NAc infusions of the muopioid receptor (MOR) agonist DAMGO moderately reinstated responding on the cocaine-paired lever at low doses (1.0-3.0 ng/side), whereas the delta-opioid receptor (DOR) agonist DPDPE induced greater responding at higher doses (300-3000 ng/side) that also enhanced inactive lever responding. Using doses of either agonist that induced responding on only the cocaine-paired lever, we found that DAMGO-induced responding CP673451 mouse was blocked selectively by pretreatment with the MOR antagonist, CTAP, whereas DPDPE-induced responding was selectively blocked by the DOR antagonist, naltrindole. Cocaine-primed reinstatement was blocked

by intra-NAc CTAP but not naltrindole, indicating a role for endogenous OICR-9429 supplier MOR-acting peptides in cocaine-induced reinstatement of cocaine-seeking behavior. In this regard, intra-NAc infusions of beta-endorphin (100-1000 ng/side) induced marked cocaine-seeking behavior, an effect blocked by intra-NAc pretreatment with the MOR but not DOR antagonist. Conversely, cocaine seeking elicited by the enkephalinase inhibitor thiorphan (1-10 mu g/side) was blocked by naltrindole but not CTAP. MOR stimulation in more dorsal caudate-putamen sites was ineffective, whereas DPDPE infusions induced cocaine seeking. Together, these findings establish

distinct roles for MOR and DOR in cocaine relapse and suggest that NAc MOR could be an important therapeutic target to neutralize the effects of endogenous beta-endorphin release on cocaine relapse. Neuropsychopharmacology (2009) 34, 1946-1957; doi: 10.1038/npp.2009.28; published online 11 March 2009″
“Severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus (CoV), is a highly communicable disease with the lungs as the major pathological target. Although Atezolizumab chemical structure SARS likely stems from overexuberant host inflammatory responses, the exact mechanism leading to the detrimental outcome in patients remains unknown. Pulmonary macrophages (M phi), airway epithelium, and dendritic cells (DC) are key cellular elements of the host innate defenses against respiratory infections. While pulmonary M phi are situated at the luminal epithelial surface, DC reside abundantly underneath the epithelium. Such strategic locations of these cells within the airways make it relevant to investigate their likely impact on SARS pathogenesis subsequent to their interaction with infected lung epithelial cells. To study this, we established highly polarized human lung epithelial Calu-3 cells by using the Transwell culture system.