Orexins are associated with drug relapse in rodents. Here, we show that acute restraint stress in mice activates lateral hypothalamic (LH) orexin neurons, increases levels of orexin A and 2-arachidonoylglycerol (2-AG) in the ventral tegmental area (VTA), and reinstates extinguished cocaine-conditioned place preference (CPP). This stress-induced reinstatement of cocaine CPP depends on type 1 orexin receptors (OX1Rs), type 1 cannabinoid receptors (CB1Rs) and diacylglycerol lipase (DAGL) in the VTA. In dopaminergic neurons of VTA slices, orexin A presynaptically inhibits GABAergic transmission. This effect is prevented by internal GDP-β-S or inhibiting OX1Rs, CB1Rs, phospholipase C or DAGL, and potentiated by inhibiting 2-AG degradation. These results suggest that restraint stress activates LH orexin neurons, releasing orexins into the VTA to activate postsynaptic OX1Rs of dopaminergic neurons and generate 2-AG through a Gq-protein-phospholipase C-DAGL cascade. 2-AG retrogradely inhibits GABA release through presynaptic CB1Rs, leading to VTA dopaminergic disinhibition and reinstatement of cocaine CPP.

No abstract

Distracted driving of a motor vehicle increases a driver's susceptibility to crash involvement. Such driving in the vicinity of highway–rail grade crossings (HRGCs) is especially perilous because the distracted driver may not be aware of the presence of an approaching train. Train-involved motor vehicle crashes invariably cause more severe injuries and greater property damage than other motor vehicle crashes. Because distracted driving at HRGCs is somewhat underresearched, the objectives of this research were to (a) investigate the occurrence of distracted motor vehicle driving at HRGCs, (b) identify characteristics of those distracted motorists, and (c) ascertain empirically factors associated with distracted driving at HRGCs. Data were collected with video recordings at six HRGCs in Nebraska and were statistically analyzed. Results showed that about one-third of drivers observed at HRGCs were distracted. The presence of intersecting roads near the crossings increased distracted driving. Drivers of multiunit trucks at HRGCs were less often distracted than other drivers at HRGCs. The presence of front-seat passengers in vehicles significantly contributed to driver distraction. Findings from the research support the need for driver education about distracted driving at HRGCs. Enforcement of distracted driving laws at HRGCs as well as strengthening of existing laws may also reduce instances of distracted driving at HRGCs.