Neuroscience
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In the present study, we asked whether multiple intrathecal injections of deltorphin II, a selective delta opioid receptor (DOPR) agonist, induced DOPR tolerance in three behavioral assays. Unilateral inflammation caused by complete Freund's adjuvant (CFA) injection into the rat or mouse hind paw (CFA model) induced thermal hyperalgesic response that was transiently and dose-dependently reduced by intrathecal administration of deltorphin II or morphine. In both rodent species, the effect of deltorphin II was not modified by a single prior administration of deltorphin II, suggesting an absence of acute tolerance in this paradigm. ⋯ In contrast to the antihyperalgesic responses, tolerance to the motoric effect of deltorphin II was evident in mice previously exposed to multiple intrathecal agonist injections, but not multiple saline administrations. Using the tail flick antinociceptive test, we found that DOPR-mediated analgesia was significantly reduced by repeated exposure to deltorphin II. Altogether, these observations suggest that repeated injections of DOPR agonists induce differential tolerance effects on antihyperalgesic, antinociceptive, and motor incoordination/ataxia-like behaviors related to DOPR activation by deltorphin II.
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The role of chemokines in immune function is clearly established. Recent evidence suggests that these molecules also play an important role in the central nervous system as modulators of neuronal activity. The chemokine CXCL12 has been identified in several regions of the adult rat brain including the substantia nigra, ventral tegmental area and caudate putamen. ⋯ Conversely, administration of CXCL12 into the lateral shell of the nucleus accumbens resulted in an inhibition of cocaine-stimulated ambulatory activity. No alterations in ambulatory or stereotypic activity were observed following CXCL12 administration into the core of the nucleus accumbens. These results demonstrate that CXCL12 can modulate the behavioral effects produced by cocaine in a brain region-specific manner.
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In Drosophila, mushroom bodies are centers for higher order behavior. Mushroom body neurons consist of three distinct types of neuronal cells, alpha, alpha'/beta', and alpha/beta, which are all generated by the same neuroblasts. ⋯ Reduced bun expression causes decreased and premature arrest of neuroblast cell division, which results in reduced numbers of alpha/beta neurons and thin axon bundled formation. We propose that bun acts as a specific factor in regulating neuroblast mitotic activity during the development of alpha/beta neurons.
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We recorded 872 single units across the complete sleep-waking cycle in the mouse preoptic area (POA) and basal forebrain (BFB), which are deeply involved in the regulation of sleep and wakefulness (W). Of these, 552 were sleep-active, 96 were waking-active, 106 were active during both waking and paradoxical sleep (PS), and the remaining 118 were state-indifferent. Among the 872, we distinguished slow-wave sleep (SWS)-specific, SWS/PS-specific, PS-specific, W-specific, and W/PS-specific neurons, the last group being further divided into specific tonic type I slow (TI-Ss) and specific tonic type I rapid (TI-Rs) both discharging specifically in association with cortical activation during both W and PS. ⋯ At the transition from SWS to W, the sleep-specific neurons showed a significant decrease in firing rate 0.1 s before the onset of cortical activation, while the W-specific and W/PS-specific neurons fired >0.5 s before the onset. TI-Ss neurons were characterized by a triphasic broad action potential, slow single isolated firing, and an antidromic response to cortical stimulation, whereas TI-Rs neurons were characterized by a narrow action potential and high frequency burst discharge in association with theta waves in PS. These data suggest that the forebrain sleep/waking switch is regulated by opposing activities of sleep-promoting (SWS-specific and SWS/PS-specific) and waking-promoting (W-specific and W/PS-specific) neurons, that the initiation of sleep is caused by decreased activity of the waking-promoting neurons (disfacilitation), and that the W/PS-specific neurons are deeply involved in the processes of cortical activation/deactivation.