MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function.

In Parkinson's disease, cognitive deficits manifest as fronto-striatally-mediated executive dysfunction, with impaired attention, planning, judgment, and impulse control. We examined changes in executive function in mice lesioned with subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a 3-choice serial reaction-time (SRT) task, which included measures of sustained attention and impulse control. Each trial of the baseline SRT task comprised a pseudo-random pre-cue period ranging from 3 to 8 s, followed by a 1-s cue duration.

Activation of type 5 metabotropic glutamate receptors and diacylglycerol lipase-α initiates 2-arachidonoylglycerol formation and endocannabinoid-mediated analgesia.

Acute stress reduces pain sensitivity by engaging an endocannabinoid signaling circuit in the midbrain. The neural mechanisms governing this process and molecular identity of the endocannabinoid substance(s) involved are unknown. We combined behavior, pharmacology, immunohistochemistry, RNA interference, quantitative RT-PCR, enzyme assays, and lipidomic analyses of endocannabinoid content to uncover the role of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) in controlling pain sensitivity in vivo.

Molecular architecture of endocannabinoid signaling at nociceptive synapses mediating analgesia.

Cannabinoid administration suppresses pain by acting at spinal, supraspinal and peripheral levels. Intrinsic analgesic pathways also exploit endocannabinoids; however, the underlying neurobiological substrates of endocannabinoid-mediated analgesia have remained largely unknown. Compelling evidence shows that, upon exposure to a painful environmental stressor, an endocannabinoid molecule called 2-arachidonoylglycerol (2-AG) is mobilized in the lumbar spinal cord in temporal correlation with stress-induced antinociception.