1,721,031 research outputs found
Serotonin blocks the long-term potentiation induced by primed burst stimulation in the CA1 region of rat hippocampal slices.
No full textThe effect of 5-hydroxytryptamine on the induction of long-term potentiation by a train of high frequency pulses (100 Hz; 1 s) or by a stimulation consisting of one burst of five pulses at 100 Hz delivered 170 ms after a single pulse (primed burst) was investigated in the CA1 region of the rat hippocampal slicein vitro with extracellular recordings. Superfusion with 5-hydroxytryptamine (3–30 μM) produced a concentration-dependent decrease in amplitude of the population spikes evoked by test stimuli. The presence of 5-hydroxytryptamine (30 μ M) did not affect the magnitude of long-term potentiation produced by the high-frequency stimulation but it prevented the long-term potentiation induced by a primed burst. The action of 5-hydroxytryptamine was mimicked by the 5-hydroxytryptamine1A agonist 5-carboxamidotryptamine (0.3 μM) and blocked by the 5-hydroxytryptamine2/5-hydroxytryptamine1a antagonist spiperone (3 μM) or by the 5-hydroxytryptamine1/5-hydroxytryptamine2 antagonist methiothepin (1–10 μM). The selective 5-hydroxytryptamine2 antagonist ritanserin (1 μM) did not antagonize the block of long-term potentiation produced by 5-hydroxytryptamine. The selective 5-hydroxytryptamine3 antagonists (3-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205–930; 1 nM) and ondansetron (GR-38032; 30 nM) did not affect the reduction in the population spike produced by application of 5-hydroxytryptamine. In contrast, a primed burst delivered at the fifth minute of 5-hydroxytryptamine application in the presence of a 5-hydroxytryptamine3 antagonist induced a long-term potentiation.
It is concluded that activation of 5-hydroxytryptamine1a and 5-hydroxytryptamine3 receptors blocked the induction of long-term potentiation induced by primed burst stimulation but not that induced by a l s high-frequency train. Given the heterogeneous localization of these receptor subtypes, it is suggested that the overall action of 5-hydroxytryptamine was exerted by hyperpolarizing pyramidal cells via 5-hydroxytryptamine1a receptors and by increasing spontaneous discharges of GABAergic interneurons via stimulation of 5-hydroxytryptamine3 receptors
Effects of rofecoxib treatment on brain inflammatory reaction and cholinergic function in beta-(1-42) injected rats into the nucleus basalis
No full textChanges in synaptosomal high affinity choline uptake following electrical stimulation of guinea-pig cortical slices: effect of atropine and physostigmine.
No full textSuperfused guinea-pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured. 2 The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU. 3 Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency-dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices. 4 The addition of atropine (1.5 x 10(-8) M) to the slices enhanced and that of physostigmine (3 x 10(-5) M) reduced the frequency-dependent increase in HACU rate. Atropine (1.5 x 10(-6) M) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone. 5 These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU
Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices
No full textThe effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate
Effects of novel NSAIDs on brain inflammation and release of neurotrasmitters in animal models of neurodegeneration
No full textEffect of the nootropic drug Oxiracetam on field potentials of rat hippocampal slices.
No full textThe effect of the nootropic drug oxiracetam on hippocampal neurotransmission was investigated in the CA1 region of the rat hippocampal slice in vitro by use of extracellular recordings. Superfusion of oxiracetam (0.1-100 μM) produced a concentration-dependent, wash-resistant (>90 min), increase in initial slope and amplitude of the dendritic field excitatory postsynaptic potential (e.p.s.p.). This increase was maximal at a concentration of 1 μM (70%). Input-output curves relating the initial slope to the amplitude of the afferent volley were significantly (P < 0.05) steeper and showed a greater maximal response in the presence of 1 μM oxiracetam than in control conditions. Two trains of high frequency stimulation (100 Hz, 0.4 s, 5 min apart) delivered in the striatum radiatum 30 min after washout of oxiracetam (1 μM) still elicited a long-term potentiation (LTP) of the field e.p.s.p. However, the absolute magnitude of the LTP produced did not differ from that obtained in untreated slices. After induction and establishment of LTP, oxiracetam (1 μM) had a smaller (27%) and reversible effect on the evoked field e.p.s.p. D-2-Amino-5-phosphonopentanoic acid (AP-5), at the same concentration (50 μM) which in our conditions prevented the induction of LTP, blocked the action of 1 μM oxiracetam and strongly depressed the effect of higher concentrations of the nootropic drug. It is concluded that oxiracetam provokes an enduring increase of neurotransmission in the CA1 rat hippocampal region. This action appears to share some features with LTP as indicated by its persistence, sensitivity to AP-5 and lack of additivity with electrically-induced LTP
NSAIDs in animal models of Alzheimer's disease
No full textBrain inflammation is an underlying factor in the pathogenesis of Alzheimer's disease (AD) and epidemiological studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of AD and may delay its onset or slow its progression. Nevertheless, recent clinical trials have shown that NSAIDs do not alter the progression of AD. Neuroinflammation occurs in vulnerable regions of the AD brain where highly insoluble β-amyloid (Aβ) peptide deposits and neurofibrillary tangles, as well as damaged neurons and neurites, provide stimuli for inflammation. To elucidate the complex role of inflammation in neurodegenerative processes and the efficacy of NSAIDs in AD we developed an animal model of neuroinflammation/neurodegeneration in vivo. An "artificial plaque" was formed by injecting aggregated β-amyloid peptide (A(1-40) or A(1-42)) into the nucleus basalis magnocellularis (NBM) of rats. We investigated several aspects of the neuroinflammatory reaction around the "artificial plaque" such as microglia and astrocyte activation, production of proinflammatory compounds, activation of cyclooxigenase-2 (COX-2), p38 Mitogen Activated Protein Kinase (p38MAPK) and induction of inducible Nitric Oxide Synthase (iNOS). Finally, degeneration of cortically projecting cholinergic neurons was also evaluated by means of immunohistochemistry and microdialysis. We examined whether the attenuation of brain inflammatory reaction by NSAIDs and NO-donors may protect neurons against neurodegeneration. The data reported in this review show that in in vivo model of brain inflammation and neurodegeneration, the administration of NSAIDs and NO-donors prevent not only the inflammatory reaction, but also the cholinergic hypofunction. Our data may help elucidating the role of neuroinflammation in the pathogenesis of AD and the ability of anti-inflammatory agents to reduce the risk of developing AD and to slow its progression
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