Neuroscience
-
Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a synthetic cannabinoid agonist illegally marketed in "Spice" and "herbal blend" for its psychoactive effect greater than those produced by cannabis. In rodents JWH-018 reproduces typical effects of (-)-Δ(9)-THC or Dronabinol® (Δ(9)-THC) such as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on sensorimotor functions are still unknown. Therefore, the aim of the present study is to investigate the effect of acute administration of JWH-018 (0.01-6mg/kg i.p.) on sensorimotor functions in male CD-1 mice and to compare its effects with those caused by the administration of Δ(9)-THC (0.01-6mg/kg i.p.). ⋯ All behavioral effects and neurological alterations were prevented by the administration of the selective CB1 receptor antagonist/inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM 251). For the first time these data demonstrate that JWH-018 impairs sensorimotor responses in mice. This aspect should be carefully evaluated to better understand the potential danger that JWH-018 may pose to public health, with particular reference to decreased performance in driving and hazardous works.
-
Tumor necrosis factor alpha (TNFα) is increased in patients with headache, neuropathic pain, periodontal and temporomandibular disease. This study and others have utilized TNF receptor 1/2 (TNFR1/2) knockout (KO) animals to investigate the effect of TNFα dysregulation in generation and maintenance of chronic neuropathic pain. The present study determined the impact of TNFα dysregulation in a trigeminal inflammatory compression (TIC) nerve injury model comparing wild-type (WT) and TNFR1/2 KO mice. ⋯ The results suggest the dysregulated serum cytokine proteome profile and bilateral spinal trigeminal nucleus microglial activation are contributory to the bilateral mechanical hypersensitization in this chronic trigeminal neuropathic pain model in the mice with TNFα dysregulation. Data support involvement of both neurogenic and humoral influences in chronic neuropathic pain.
-
Impulsive actions and decisions often lead to undesirable outcomes. Lesion and neuroimaging studies have revealed that the orbital frontal cortex (OFC) and dorsal striatum (dSTR) play key roles in inhibitory control. It has been proposed that greater OFC input into the dSTR reflects enhanced top-down cognitive control and less impulsive responding. ⋯ BDA was visualized using histochemistry followed by light microscopy imaging and densitometry analysis. Density of BDA in the dSTR was significantly greater in females as compared to males indicating that the projections from the OFC to dSTR may be greater in females as compared to males. Our results suggest a potential neuroanatomical sex difference that may contribute to the reported differences in inhibitory control levels of male and female rats.
-
Activation of peroxisome proliferator-activated receptors (PPARs), namely PPARγ and PPARδ, has been shown to provide neuroprotection in a number of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease (PD). The observed neuroprotective effects in experimental models of PD have been linked to anti-oxidant and anti-inflammatory actions. This study aimed to analyze the full influence of these receptors in neuroprotection by generating a nerve cell-specific conditional knock-out of these receptors and subjecting these genetically modified mice to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to model dopaminergic degeneration. ⋯ Presence of one or both these receptors show a trend toward protection against this degeneration, as higher dopaminergic cell immunoreactivity and striatal monoamine levels are evident. These data supplement recent studies that have elected to use agonists of the receptors to regulate immune responses. The results place further importance on the activation of PPARs and the neuroprotective roles these have in inflammatory processes linked to neurodegenerative processes.
-
Strength training of one limb results in a substantial increase in the strength of the untrained limb, however, it remains unknown what the corticospinal responses are following either eccentric or concentric strength training and how this relates to the cross-education of strength. The aim of this study was to determine if eccentric or concentric unilateral strength training differentially modulates corticospinal excitability, inhibition and the cross-transfer of strength. ⋯ The results show that eccentric training uniquely modulates corticospinal excitability and inhibition of the untrained limb to a greater extent than concentric training. These findings suggest that unilateral eccentric contractions provide a greater stimulus in cross-education paradigms and should be an integral part of the rehabilitative process following unilateral injury to maximize the response.