Brain research
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Comparative Study
Intra-amygdalar injection of DAMGO: effects on c-Fos levels in brain sites associated with feeding behavior.
It is well known that the mu opioid agonist, Tyr-D-Ala-Gly-(me) Phe-Gly-ol (DAMGO), increases food intake in rats when injected into a variety of brain sites including the central nucleus of the amygdala (CeA). Immunohistochemical studies measuring c-Fos immunoreactivity (IR) suggest that the CeA contributes to opioid-related feeding. In the current study, we injected 2 nmol of DAMGO and measured food intake, c-Fos IR levels in various brain sites involved in feeding behavior, and mu opioid receptor internalization. ⋯ Administration of DAMGO into the CeA increased c-Fos IR levels in the shell of the nucleus accumbens (NAcc), but not in 17 other brain sites that were studied. We also found that intra-CeA injection of DAMGO, prior to LiCl injection, decreased c-Fos IR levels in the CeA compared to vehicle-injected rats. Thus, intra-CeA administration of DAMGO may increase feeding, in part, by activating neurons in the shell of the nucleus accumbens and by inhibiting activity of selected neurons in the CeA.
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Comparative Study Clinical Trial
The effects of muscle vibration on anticipatory postural adjustments.
The current study investigated the influence of changes in sensory information related to postural stability on anticipatory postural adjustments (APAs) in standing subjects. Subjects performed fast arm movements and a load release task while standing on a stable force platform or on an unstable board. We manipulated sensory information through vibration of the Achilles tendons and additional finger touch (contact forces under 1 N). ⋯ Small changes in the other index related to reciprocal activation (R-index) were found only in trunk muscles. Light touch and vibration induced opposing changes in the C-index, suggesting their opposite effects on the stabilization of a reference point or vertical. We conclude that the central nervous system deploys patterns of adjustments in which increased co-contraction of distal muscles and reciprocal adjustments in trunk muscles are modified to ensure equilibrium under postural instability.
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Comparative Study
Macrokinetic analysis of blockade of NMDA-gated currents by substituted alcohols, alkanes and ethers.
Volatile hydrocarbon based CNS depressants including short chain alcohols and anesthetics act, in part, by inhibition of the excitatory effect of glutamate at the NMDA receptor. While effects of several of these volatile agents on NMDA-gated currents have been demonstrated, there has been no direct comparison of different chemical classes of CNS depressant drugs on NMDA-gated currents. Here, whole-cell voltage clamp measurements of currents gated by 100 microM NMDA from cultured cerebrocortical neurons were examined in the presence of varying concentrations of the alcohols ethanol and hexanol, the halogenated alcohol trichloroethanol, the halogenated alkane halothane and the halogenated ethers isoflurane and sevoflurane. ⋯ Onset kinetics for the CNS depressants was similar with tau values near 100 ms. Offset kinetics was more variable with tau ranging from 88.2 ms for ethanol to 221.4 ms for trichloroethanol. These data indicate that a wide variety of volatile hydrocarbon based CNS depressants produce a similar inhibition of NMDA-gated currents and that the kinetics for these agents are inconsistent with an open channel block.
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Comparative Study
Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons.
Glutamate-induced excitotoxicity is implicated as playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), and mitochondrial dysfunction is also found in ALS patients. We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord. Rotenone and malonate induced relatively selective toxicity against motor neurons as compared to non-motor neurons, whereas antimycin caused non-selective toxicity. ⋯ When mitochondrial complex I was mildly inhibited by a sub-lethal concentration of rotenone, AMPA-induced motor neuron death was significantly exacerbated. A sub-lethal concentration of malonate exacerbated both NMDA- and AMPA-induced motor neuron death. These data suggest that mitochondrial dysfunction predisposes motor neurons to ionotropic glutamate receptor-mediated excitotoxicity.
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Morphine analgesic potency following systemic administration was assessed in male and female mice undergoing prior and repeated intrathecal morphine injections. Although morphine ED50 values were significantly increased in both sexes relative to their respective saline-injected controls, the magnitude of tolerance was greater in females. Intrathecal injection alone had no effect on morphine analgesia. The data suggest that spinal mechanisms contribute to sex differences in analgesic tolerance following systemic morphine administration.