Neuroscience
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Cocaine's (COC) direct interaction with the dopamine (DA) transporter is usually considered the most important action underlying the psychomotor stimulant and reinforcing effects of this drug. However, some physiological, behavioral and psycho-emotional effects of COC are very rapid and brief and they remain intact during DA receptor blockade, suggesting possible involvement of peripheral non-DA neural mechanisms. To assess this issue, single-unit recording with microiontophoresis was used to examine changes in impulse activity of dorsal and ventral striatal neurons to i.v. ⋯ While the nature of these neuronal elements needs to be clarified using other analytical techniques, they might involve voltage-gated K(+) and Na(+) channels, which have a high affinity for COC and are located on terminals of visceral sensory nerves that densely innervate peripheral vessels. Therefore, along with direct action on specific brain substrates, central excitatory effects of COC may occur via indirect action, involving afferents of visceral sensory nerves and rapid neural transmission. By providing a rapid sensory signal and triggering transient neural activation, such a peripherally triggered action might play a crucial role in the sensory effects of COC, thus contributing to learning and development of drug-taking behavior.
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A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke.
Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. ⋯ Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-x(L) in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-x(L) following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex.
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The amygdala is a medial forebrain structure with an established role in nociceptive modulation, including the expression of stress-induced hypoalgesia (SIH). Projections from the locus coeruleus increase levels of noradrenaline in the amygdala during acute stress. alpha(2)-Noradrenergic receptor agonists have significant clinical utility as analgesic agents. We therefore hypothesized that alpha(2)-noradrenergic activation of the amygdala may result in behaviorally measurable hypoalgesia. ⋯ When injected alone, no antagonist resulted in a significant change in TFL compared with baseline. Clonidine injection into the amygdala but outside the CeA, including the basolateral nucleus of the amygdala, did not significantly alter TFL. These results demonstrate that anatomically and pharmacologically specific activation of alpha(2)-receptors in the CeA in lightly anesthetized rats results in behaviorally measurable antinociception.
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This study investigated whether somatostatin (SST) modulates the excitability of nociceptive trigeminal ganglion (TRG) neurons that innervate the nasal mucosa and project to the upper cervical (C(1)) dorsal horn by using perforated-patch clamping, retrograde-labeling, and immunohistochemistry. Fluorogold (FG) retrograde labeling was used to identify the rat TRG neurons innervating the nasal mucosa, while microbeads (MB) were used to label neurons projected onto the superficial layer of the C(1) dorsal horn. FG-labeled small-diameter TRG neurons exhibited SST(2A) receptor immunoreactivity (19%) and half of these neurons were also labeled with MB. ⋯ Under voltage-clamp conditions, SST (1 microM) significantly increased the voltage-gated K(+) transient (I(A)) and sustained (I(K)) currents and these increases were abolished by coapplication of CYN154806 (1 microM). In the presence of both 4-aminopyridine (6 mM) and tetraethylammonium (10 mM), no significant changes in the membrane potential in response to SST application were found. These results suggest that modulation of trigeminal nociceptive transmission in the C(1) dorsal horn by activation of SST(2A) receptors occurs at the level of small-diameter TRG cell bodies and/or their afferent terminals, and that this may be related to regulation of protective upper-airway reflexes.