Neuroscience
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The basolateral amygdala (BL) is a putative site for regulating anxiety, where inhibition and excitation respectively lead to decreases and increases in anxiety-like behaviors. The BL contains local networks of GABAergic interneurons that are subdivided into classes based on neurochemical content, and are hypothesized to regulate unique functional responses of local glutamatergic projection neurons. Recently it was demonstrated that lesioning a portion of the BL interneuronal population, those interneurons that express neurokinin1 receptors (NK(1r)), resulted in anxiety-like behavior. ⋯ In addition to enhancing the phenotypic characterization, the extent to which the NK(1r) cells of amygdala nuclei contribute to anxiety-like responses was also investigated. Lesioning the NK(1r) expressing interneurons, with a stable form of substance P (SSP; the natural ligand for NK(1r)) coupled to the targeted toxin saporin (SAP), in the anterior and posterior divisions of the BL was correlated to increased anxiety-like behaviors compared to baseline and control treated rats. Furthermore the phenotypic and regional selectivity of the lesions was also confirmed.
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Tumor necrosis factor-alpha (TNF) is a pro-inflammatory cytokine that is implicated in the initiation of neuropathic pain. Locally administered TNF antagonist etanercept offers a promising new treatment approach to target neuropathic pain. Here we evaluate the distribution and binding specificity for TNF isoforms of locally administered etanercept into injured and uninjured rat sciatic nerve. ⋯ Finally, locally administered etanercept inhibited pain-related behaviors in a rat sciatic nerve crush model. We conclude that locally administered etanercept reaches the endoneurial space in the injured nerve and preferentially binds to transmembrane and bioactive trimer TNF isoforms to modulate neuropathic pain. Locally administered etanercept has potential as a targeted immunomodulating agent to treat local pathogenesis in neuropathic pain after peripheral nerve injury.
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Current theories of neuropathic hypersensitivity include an imbalance of supraspinal inhibition and facilitation. Our overall hypothesis is that the locus coeruleus (LC), classically interpreted as a source of pain inhibition, may paradoxically result in facilitation after tibial and common peroneal nerve transection (spared sural nerve injury--SNI). We first tested the hypothesis that non-noxious tactile hind paw stimulation of the spared sural innervation territory increases neuronal activity in the LC in male rats. ⋯ Lidocaine reduced all behavioral signs of neuropathic pain in a reversible manner, suggesting that the LC contributes to pain facilitation. We conclude that, in addition to its well-known inhibition of acute and inflammatory pain, the LC facilitates the development and maintenance of neuropathic pain in the SNI model. Further studies are needed to determine the facilitatory pathways emanating from the LC.
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The perioculomotor urocortin-containing population of neurons (pIIIu: otherwise known as the non-preganglionic Edinger-Westphal nucleus) is sensitive to alcohol and is involved in the regulation of alcohol intake. A recent study indicated that this brain region is also sensitive to psychostimulants. Since pIIIu has been shown to respond to stress, we investigated how psychostimulant-induced pIIIu activation compares to stress- and ethanol-induced activation, and whether it is independent from a generalized stress response. ⋯ In both mice and rats, ethanol- and cocaine-induced Fos immunoreactivity occurred exclusively in urocortin 1-positive, but not in tyrosine hydroxylase-positive, cells. These results provide evidence that the pIIIu Fos-response to psychostimulants is independent of a generalized stress in mice, but not rats. They additionally show that the pIIIu response to stress differs significantly between species.
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Adolescence may be a critical period for drug addiction. Young adolescent male rats have greater locomotor responses than adults after acute low dose cocaine administration. Further, repeated cocaine administration produces as much or more conditioned place preference but reduced locomotor sensitization in adolescents compared to adults. ⋯ Finally, there was a significant correlation between the expression of c-fos and zif268 in the adult striatum but not in adolescents. Our results suggest that the coordinated expression of transcription factors by cocaine continues to develop during adolescence. The immature regulation of transcription factors by cocaine could explain why adolescents show unique sensitivity to specific long-term behavioral alterations following cocaine treatment.