Neuroscience
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These experiments explore the role of 5-HT1A receptors in the regulation of cell proliferation in the dentate gyrus of the intact and adrenalectomized adult rat. Depleting 5-HT with p-chlorophenylalanine (300 mg/kg initially followed by 100 mg/kg/day) or stimulating 5-HT1A receptors with 8-OH-DPAT (1 mg/kg or 2 mg/kg, s.c. injections twice daily) for 14 days had no effect on cell proliferation as measured by Ki-67 or BrdU (5-bromo-3-deoxyuridine) immunocytochemistry in the dentate gyrus. However, combined treatment with p-chlorophenylalanine followed by 8-OH-DPAT significantly increased cell proliferation compared with p-chlorophenylalanine alone. ⋯ The 5-HT1A antagonist WAY-100635 (1.5 mg/kg/day also delivered by osmotic pump) by itself did not alter cell proliferation, confirming that reduced serotonin activity does not change proliferation, but blocked the effect of 8-OH-DPAT. However, WAY-100635 could not block the stimulating action of adrenalectomy cell proliferation. 5-HT1A mRNA expression was not altered in the hippocampus by adrenalectomy. Thus, the effect of adrenalectomy on cell proliferation and survival is not 5-HT1A dependent, despite the interaction between 5-HT1A and corticosterone.
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Comparative Study
Opposite behaviours in the forced swimming test are linked to differences in spatial working memory performances in the rat.
Despite consistent evidence of an association between depression and impaired memory performance, only a few studies have investigated memory processes in animal models of depression. The aim of the present study was to determine if rats selected for marked differences in their immobility response in the forced swimming test (FST, i.e. high-immobility, [HI] and low-immobility [LI] rats) exhibit differences in spatial and non-spatial memory performances. In a classic radial maze elimination task, we observed that HI rats made significantly more errors than LI rats, and their first error appeared significantly earlier. ⋯ On the other hand, performances in the two groups of animals were similar in a non-spatial task, the object recognition task. Complementary behavioral data indicate that the differences observed between the two groups are not attributable to opposite locomotor activities or to different levels of anxiety. Overall we can conclude that opposite swimming behavior in the FST could parallel some differences in cognitive performances, more specifically linked to spatial working memory.
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Comparative Study
Spinal phospholipase A2 in inflammatory hyperalgesia: role of the small, secretory phospholipase A2.
Current work emphasizes that peripheral tissue injury and inflammation results in a heightened sensitivity to subsequent noxious input (hyperalgesia) that is mediated in large part by the spinal synthesis and release of eicosanoids, in particular prostaglandins. Secreted phospholipase A(2)s (sPLA(2)s) form a class of structurally related enzymes that release arachidonic acid from cell membranes that is further processed to produce eicosanoids. We hypothesized that spinal sPLA(2)s may contribute to inflammation-induced hyperalgesia. ⋯ IT LY311727 also suppressed thermal hyperalgesia induced by IT injection of substance P (30 nmol). Using in vivo spinal microdialysis, we found that IT injection of LY311727 attenuated prostaglandin E(2) release into spinal dialysate otherwise evoked by the IT injection of substance P. Taken together, this work points to a role for constitutive sPLA(2)s in spinal nociceptive processing.
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Endothelin-1 (ET-1) exists in endothelial cells as well as a variety of other cell types. The presence of ET-1 and its receptors in neurons suggests its possible role as a neurotransmitter and/or neuromodulator. Studies utilizing exogenous ET-1 have suggested that ET-1 affects pain transmission. ⋯ To confirm that ET-1 is released in persistent pain states and to determine which part of the CNS is involved, we measured the concentrations of ET-1 before and after inducing peripheral inflammation in different parts of the CNS involved in endogenous pain inhibitory systems in normal mice. We found that ET-1 was increased in the hypothalamus while no significant increase was observed in the midbrain, medulla and spinal cord. The results of the present study suggest that neuronal ET-1 is involved in endogenous pain inhibitory control likely via pathways through the hypothalamus.
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Comparative Study
Fear learning transiently impairs hippocampal cell proliferation.
We sought to determine whether contextual fear conditioning, a hippocampal-dependent task, would affect neurogenesis in the dentate gyrus of the hippocampus, and if so, to identify which aspect of the training experience accounts for the change. The immediate shock deficit paradigm was used, together with bromodeoxyuridine immunohistochemistry, to isolate the contribution of different aspects of contextual fear conditioning to neurogenesis. ⋯ This attenuation was not related to exposure to the conditioned stimulus alone, the footshock unconditioned stimulus alone, or the expression of fear to the context after training. Instead, the effect of context conditioning on cell proliferation appears to be specifically due to the formation of an association between the context and shock during training, an amygdala dependent function.