Neuroscience
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The α2 adrenergic receptor antagonist yohimbine (YO) is a sympathomimetic drug that crosses the blood-brain barrier after systemic administration. YO promotes increased transmitter release from noradrenergic (NA) axon terminals in the central nucleus of the amygdala (CEA), bed nucleus of the stria terminalis (BST), hypothalamus, and other brain regions implicated in physiological and behavioral responses to stressful and threatening stimuli. YO is potently anxiogenic in humans and experimental animals, including rats. ⋯ The ability of YO to increase anxiety-like behavior in the EPMZ was similarly robust in rats with sham lesions or ipsilateral CEA-algBST lesions. Conversely, YO anxiogenesis in the EPMZ was disrupted in rats with asymmetric lesions designed to bilaterally disconnect the CEA and algBST, whereas neither unilateral nor bilateral disconnecting lesions altered EPMZ behavior in rats after i.p. saline. We conclude that the anxiogenic effects of increased NA signaling in rats after YO require direct CEA-algBST interactions that do not shape EPMZ behavior under baseline conditions.
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In the present study, multielectrode array (MEA) recording was used to illustrate the spatial-temporal progression of anterior cingulate cortex (ACC) activity following stimulation of the thalamus in a thalamocingulate pathway-preserved slice. The MEA was placed under the slice that contained the ACC, and 60 channels of extracellular local field potentials evoked by bipolar electrical stimulation within the thalamus were analyzed. Several distinct thalamic-evoked responses were identified. ⋯ The thalamus-evoked responses were activated and progressed along a deep surface-deep trajectory loop across the ACC layers. Glutamatergic neurotransmitters were crucially involved in information processing. Opioid interneurons may play a modulatory role in regulating the signal flows in the cingulate cortex.
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Exposure to ethanol during the prenatal period contributes to increased alcohol consumption and preference in rodents and increased risk for alcoholism in humans. With studies in adult animals showing the orexigenic peptides, enkephalin (ENK), galanin (GAL) and orexin (OX), to stimulate ethanol consumption, the question addressed here is whether prenatal ethanol alters the development in utero of specific neurons that express these peptides. With reports describing suppressive effects of high doses of ethanol, we examined the offspring of dams gavaged from embryonic day 9 to parturition with a control solution or lower ethanol doses, 1 and 3g/kg/day, known to promote ethanol consumption in the offspring. ⋯ These BrdU-positive neurons were found to express ENK, GAL and OX, indicating that prenatal ethanol promotes neurogenesis in these specific peptide systems. There were no changes in gliogenesis or apoptosis. This increase in neurogenesis and density of peptide-expressing neurons suggests the involvement of these hypothalamic and accumbal peptide systems in mediating the increased alcohol consumption observed in prenatal ethanol-exposed offspring.
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In heterozygous mice, attenuation of G-protein-coupled receptor kinase 2 (GRK2) level in nociceptors is associated with enhanced and prolonged inflammatory hyperalgesia. To further elucidate the role of GRK2 in nociceptor function we reversibly decreased GRK2 expression using intrathecal antisense oligodeoxynucleotide (AS-ODN). GRK2 AS-ODN administration led to an enhanced and prolonged hyperalgesia induced by prostaglandin E(2), epinephrine and carrageenan. ⋯ Unlike hyperalgesic priming induced by transient activation of protein kinase C epsilon (PKCε), (Aley et al., 2000; Parada et al., 2003b), the enhanced and prolonged hyperalgesia following attenuation of GRK2 is PKCε- and cytoplasmic polyadenylation element binding protein (CPEB)-independent and is protein kinase A (PKA)- and Src tyrosine kinase (Src)-dependent. Finally, rats treated with GRK2 AS-ODN exhibited enhanced and prolonged hyperalgesia induced by direct activation of second messengers, adenyl cyclase, Epac or PKA, suggesting changes downstream of G-protein-coupled receptors. Because inflammation can produce a decrease in GRK2, such a mechanism could help explain a predilection to develop chronic pain, after resolution of acute inflammation.