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【越障1-3】昨天没时间看了,今天补上
<span style="color:#4b0082;"><font face="Verdana, sans-serif">Today's topic:</font></span><span style="color:#4b0082;"><font face="Verdana, sans-serif"> </font></span><span style="color:#4b0082;"><font face="Verdana, sans-serif">Rapid visuallearning in the rat: Effects at the 5-HT</font></span><span style="color:#4b0082;"><font size="1"><font face="Verdana, sans-serif">1a</font></font></span><span style="color:#4b0082;"><font face="Verdana, sans-serif"> </font></span><span style="color:#4b0082;"><font face="Verdana, sans-serif">receptorsubtype</font></span><span style="color:white;"><font face="Verdana, sans-serif">( Z3 r$K! X2 q% q* T</font></span><span style="color:#4b0082;"><font face="Verdana, sans-serif"><br /><br /></font></span><span style="color:#444444;"><font size="4">The5-hydroxytryptamine</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">(5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4">) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT; 0.15 mg/kg) impaired rats’ rapid visual learning on acomputerized maze.This treatment also increased decision time (DT) but thelearning impairment was not necessarily a side-effect of slower respondingbecause, in this task,responses made at long DT are more accurate than those atshort DT. The selective 5-HT1a receptor antagonist WAY±100635 (0.3mg/kg) wasitself without effect on accuracy, but was effective in reversing effects of 8-OH-DPAT(on both accuracy and DT). Within problems (i.e., over the 40±60 rials of asingle discrimination), performance was reduced by treatment with 8-OH-DPAT at</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">all stages of learning.We conclude that this effect is mediated through the 5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor site (ratherthan through some other serotonergic receptor site or non-specific mechanism)as it was reversible by treatment with WAY±100635.Although it could still arisefrom behaviourally non-specific effects, the performance deficit finds its bestaccount in terms of the psychological processes necessary to visual learning.Its reversal with WAY±100635 offers support to the hypothesis that 5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor antagonistscould improve cognitive function, under conditions of pre-existing impairmentdue to overactive serotonergic inhibition, as is thought to occur inAlzheimer’s disease.</font></span><span style="color:#444444;"><br /><br /></span><span style="color:#444444;"><font size="4">Theserotonergic (5-hydroxytryptamine, 5-HT) system is implicated in normallearning and in impairments of learning due to ageing and dementia (Altman&Normile, 1988; McEntee & Crook, 1991). Thus antagonists at the5-HT1areceptor site could provide a mechanism to increase the function ofcortical pyramidal cells in Alzheimer’s disease (e.g., Bowen, Francis,Pangalos,Stephens, & Proctor, 1992; Francis, Sims, Procter, & Bowen,1993). Such antagonists might work by blocking the tonic hyperpolarizingeffects of endogenous5-HT and thus enhance glutamatergic excitation infunctioning cells (Dijk, Francis,Stratmann, & Bowen, 1995). Further, innormal animals, 5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor agonists like8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) might similarly ``switchoff ’’ cortical pyramidal neurones and result in cognitive deficits (Francis etal., 1993).</font></span><span style="color:white;">7 L+ W5 C1 {4 P G</span><span style="color:#444444;"><br /><br /></span><span style="color:#444444;"><font size="4">Wepreviously found that 8-OH-DPAT impaired visual learning as measured bydiscriminative accuracy, independent of its effects on response time, which wasused as a measure of non-specific effects (Cassaday &Gaffan, 1996).However,8-OH-DPATis now known to bind 5-HT7 receptor sites (Shen et al., 1993).To define further the relevant receptor subtypes, in the present study wetested whether 8-OH-DPAT’s effects in this task are reversible by treatmentwith a5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor antagonist. WAY±100635 is 100-foldselective for the 5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor site relative to its binding at other sites(Forster et al., 1995).</font></span><span style="color:white;">+ H: k3 \" Y! D, p! d' p9 f</span><span style="color:#444444;"><br /></span><span style="color:white;">9S u! C, l9 J* c g</span><span style="color:#444444;"><br /></span><span style="color:#444444;"><font size="4">Although5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor antagonists have been shown to block anumber of 8-OH-DPAT effects (Fletcher et al., 1996), there have been relativelyfew clear demonstrations that 8-OH-DPAT has cognitive effects (but see Carli&Samanin, 1992), and a number of studies have highlighted the difficulty indissociating cognitive effects from non-specific effects on performancewhen8-OH-DPAT is given systemically (e.g., Stanhope, McLenachan, &Dourish,1995; Warburton, Harrison, Robbins, & Everitt, 1997). Given thisdifficulty,there is scant evidence that cognitive effects of 8-OH-DPAT areblocked bypre-treatment with selective 5-HT</font></span><span style="color:#444444;"><font size="1">1a</font></span><span style="color:#444444;"><font size="4"> </font></span><span style="color:#444444;"><font size="4">receptor antagonists.Carli and Samanin(1992) found that 8-OH-DPAT impaired spatial learning in thewater maze and went on to demonstrate that spatial impairment could bedemonstrated by(intrahippocampal) 8-OH-DPAT treatment that was without effecton visual learning in the same water maze task (Carli, Luschi, Garofalo, &Samanin,1995). This dissociation suggests that the spatial impairment was notsimply a consequence of non-specific deleterious effects of the 8-OH-DPATtreatment.</font></span><span style="color:#444444;"><br /><br /></span><span style="color:#444444;"><font size="4">Inthe present study, we assessed the effect of systemic 8-OH-DPAT and WAY± 100635using exactly the same paradigm and apparatus as previously (constant-negativediscrimination training in a computer-controlled Y-maze, Cassaday & Gaffan,1996), to allow direct comparison. In this procedure, rats learn a series ofdiscrimination problems in which the stimuli are complex, wide-angle visualdisplays (``scenes’’)drawn from a large population. Each problem consists of aseries of trials in which the rat chooses between two scenes: the constant,which is the same on every trial, and the variable, which is different on everytrial. Food reward is given for choosing the variable not the constant.</font></span><span style="color:white;">' ^; U' t% k, Y.H }$ I: k</span><span style="color:#444444;"><br /></span><span style="color:white;">+ H%p7 E" Y2 b o! W. ^( L</span><span style="color:#444444;"><br /></span><span style="color:#444444;"><font size="4">Wetested pigmented rats of two strains, Dark Agouti (DA) and Hooded Lister (HL).HLsare less proficient than DAs at visual learning (Aggleton, 1996; Gaffan&Eacott, 1995) so it was necessary to give them a slightly less demandingversion of the task in order to maintain constant discrimination and to keepthe baseline performance comparable to that of the DAs. Thus the DAs learnedtwo new problems per session for 40 trials each (a similar procedure to that ofCassaday &Gaffan, 1996), whereas the HLs had only one new problem persession for 60 trials. We analysed to check that drug effects were consistentacross the groups.</font></span><span style="color:#444444;"><br /><br /></span><span style="color:#444444;"><font size="4">Itis important to dissociate the motor side-effects of a drug such as8-OH-DPATfrom its effects on learning per se. In our apparatus, accuracy ofdiscrimination varies with decision latency, faster responses being lessaccurate than slower responses (Cassaday & Gaffan, 1996; Gaffan&Eacott, 1997). 8-OH-DPAT can affect response time, lengthening orshortening it at different doses, and such effects must be compensated for whenassessing whether a particular dose of the drug changes choice accuracy duringdiscrimination learning. Cassaday and Gaffan (1996) developed a method ofpartialling out the effects of a drug on speed of responding from its effect ondiscrimination.<br /><br />9min,没怎么看懂..T T再看一遍<br /><br /></font></span><span style="color:white;"> </span> |
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