The European journal of neuroscience
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Comparative Study
Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats.
Cannabinoid 2 (CB2) receptor mediated antinociception and increased levels of spinal CB2 receptor mRNA are reported in neuropathic Sprague-Dawley rats. The aim of this study was to provide functional evidence for a role of peripheral, vs. spinal, CB2 and cannabinoid 1 (CB1) receptors in neuropathic rats. Effects of the CB2 receptor agonist, JWH-133, and the CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), on primary afferent fibres were determined by calcium imaging studies of adult dorsal root ganglion (DRG) neurons taken from neuropathic and sham-operated rats. ⋯ Spinal ACEA inhibited mechanically evoked responses of neuropathic and sham-operated rats, these effects were blocked by SR141716A (0.01 microg/50 microL). Our data provide evidence for a functional role of CB2, as well as CB1 receptors on DRG neurons in sham and neuropathic rats. At the level of the spinal cord, CB2 receptors have inhibitory effects in neuropathic, but not sham-operated rats suggesting that spinal CB2 may be an important analgesic target.
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It is well-established that light pulses regulate components of the extracellular signal-regulated kinases I/II (ERK) cascade in the suprachiasmatic nuclei (SCN) circadian clock. These events are important for photic-resetting of the circadian clock. The SCN circadian clock is also reset by pulses of dark, but it is unknown if this stimulus alters the activity of ERK, the transcription factor Elk-1 or expression of the immediate early gene c-fos in the SCN. ⋯ When given at the beginning of the subjective night (CT13), a 6-h dark pulse did not phase-shift behavioural rhythms and failed to alter the expression of c-Fos, P-ERK, or P-Elk-1 in the SCN. At the level of the visual thalamus, expression of c-Fos in the intergeniculate leaflet was higher during the subjective night as compared to the subjective day, although dark pulses had no robust effects on expression of c-Fos or P-ELK-1 in this structure. We conclude that dark-pulse resetting of the circadian clock is complex and involves both non-photic and photic components.
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Comparative Study
Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8.
To study the role of the metabotropic glutamate receptor 8 (mGluR8), mice lacking this receptor were generated by homologous recombination. Homozygous mGluR8-deficient mice are about 8% heavier than their wild-type age-matched controls after reaching 4 weeks of age. This weight difference is not caused by an altered food intake and is not exacerbated by feeding the animals a high-fat diet. ⋯ By contrast, there were no genotype differences in locomotor activity in the open field, plus maze, or in total time spent exploring objects during object recognition tests, indicating that there is a dissociation between effects of mGluR8 deficiency in exploratory activity in a novel safe enclosed environment vs. a more anxiogenic novel open environment. The absence of mGluR8 also leads to increased measures of anxiety in the open field and elevated plus maze. Whether the diverse phenotypic differences observed in mGluR8-/- mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined.
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Memory impairments, which occur regularly across species as a result of ageing, disease (such as diabetes mellitus) and psychological insults, constitute a useful area for investigating the neurobiological basis of learning and memory. Previous studies in rats found that induction of diabetes (with streptozotocin, STZ) impairs long-term potentiation (LTP) but enhances long-term depression (LTD) induced by high- (HFS) and low-frequency stimulations (LFS), respectively. Using a pairing protocol under whole-cell recording conditions to induce synaptic plasticity at Schaffer collateral synapses in hippocampal CA1 slices, we show that LTD and LTP have similar magnitudes in diabetic and age-matched control rats. ⋯ In addition, compared with naïve synapses, prior induction of LTP produces a 10 mV leftward shift in Vms for inducing subsequent LTD in control but not in diabetic rats. This could indicate that diabetes acts on synaptic plasticity through mechanisms involved in metaplasticity. Persistent facilitation of LTD and inhibition of LTP may contribute to learning and memory impairments associated with diabetes mellitus.