Scopolamine model of delirium in rats and reversal of the performance impairment by aniracetam

Nakamura, Kazuo; Kurasawa, Mitsue; Tanaka, Yushiro

doi:10.1002/(sici)1098-2299(199802)43:2<85::aid-ddr1>3.0.co;2-l

Cited by 20 publications

(12 citation statements)

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“…If the compound enhances feeding behaviour in the fasted rats, CRT (response speed) would probably be shortened and the % omission decreased. A prefeeding experiment, however, has shown the present task to be relatively resistant to alterations in food motivation (Nakamura et al 1998a). Secondly, 8-OH-DPAT caused a severe 5-HT behavioural syndrome (flat body posture, reciprocal forepaw treading, salivation and defecation) and hypothermia, most of which are thought to be mediated by a direct stimulation of postsynaptic 5-HT 1A receptors (Tricklebank et al 1985), thereby reducing motor activity associated with the task performance.…”

Section: Discussionmentioning

confidence: 77%

“…The 8-OH-DPAT-induced performance impairments may be explained in relation to appetite, 5-HT behavioural syndrome or anxiolytic/antidepressive effects, since each behavioural measure reflects different or combined psychological properties (attention, vigilance/arousal, food motivation) and motor abilities of the tested animals as detailed previously (Nakamura et al 1998a). Firstly, 8-OH-DPAT elicits hyperphagia (Hoyer et al 1994;Leonard 1996).…”

Section: Discussionmentioning

confidence: 99%

“…There is no evidence suggesting direct interaction of aniracetam and its metabolites with 5-HT 1 , 5-HT 2A and 5-HT 3 receptor subtypes (Martin and Haefely 1993;Tanaka et al 1998). In addition to the serotonergic mechanism, the cholinergic activation mechanism of both drugs potentially may also be involved in the improvement of attention deficits and low vigilance (Kawajiri et al 1990;Nakamura and Shirane 1999), since reticulothalamic and cortical cholinergic projections have fundamental roles in attentional and vigilance processes (Robbins 1997;Nakamura et al 1998a). Moreover, involvement of the serotonergic-cholinergic interaction is suggested by the following: activation of 5-HT 1A receptors aggravates scopolamine-induced cognitive impairments, inhibits carbachol-stimulated phosphoinositide turnover, down-regulates muscarinic M 2 receptors (Claustre et al 1991;Riekkinen 1994) and decreases acetylcholine release (Rada et al 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The choice reaction apparatus consisted of 14 two-lever operant conditioning chambers (Skinner boxes) enclosed in wooden, sound-attenuating compartments. The basic equipment and interface-controller system are detailed elsewhere (Nakamura et al 1998a). Briefly, rats were trained daily (Monday through Friday) for 1-2 months from the age of 9-10 months.…”

Section: Methodsmentioning

confidence: 99%

“…The compound was first characterized in animal models as a learning and memory enhancer, and thought to act through mechanisms such as positive modulation of cholinergic and glutamatergic nervous systems and an increase in synaptic efficacy and energy metabolism (Himori et al 1992;Martin and Haefely 1993;Pizzi et al 1993). We have reported recently that both scopolamine and apomorphine cause attentional deficits and low vigilance in rats that had mastered previously a two-lever choice reaction task, and that aniracetam reverses the induced performance impairments (Nakamura et al 1998a(Nakamura et al , 1998b. As yet, however, no studies have evaluated experimentally the interaction between aniracetam and serotonergic compounds on attention and vigilance.…”

Section: Kazuo Nakamura · Mitsue Kurasawamentioning

confidence: 98%

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Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Nakamura¹,

Kurasawa²

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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Central serotonergic systems play an important role in regulating mood/emotion, cognition, sleep and wakefulness, appetite and locomotion and body temperature via multiple receptor subtypes. Among them, 5-HT1A and 5-HT2A/2C receptors have opposite effects with respect to certain functions. The aim of the present study was to compare the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2A/2C receptor agonist, on the performance of middle-aged rats in a two-lever choice reaction task that assessed attention and vigilance functions. We also examined the effects of aniracetam, a cognition enhancer, and its major metabolites on the induced performance impairments. 8-OH-DPAT (0.3 mg/kg s.c.) reduced response speed and choice accuracy and increased response omission with a reduction of task-associated motor activity without inducing motor inability or motivational changes. These findings indicate a specific disturbance of attentional and vigilance processes. DOI caused similar impairments at the highest dose tested (3 mg/kg s.c.); at a lower dose (1 mg/kg s.c.), however, it selectively attenuated the response speed, suggesting a selective attention deficit. (-)-Alprenolol, a non-selective 5-HT1A receptor antagonist, and ritanserin, a preferential 5-HT2A receptor antagonist, blocked the 8-OH-DPAT- and DOI-induced performance impairments respectively. Aniracetam ameliorated all the performance deficits, and the metabolites N-anisoyl-GABA and 2-pyrrolidinone partially mimicked the aniracetam effect in the 8-OHDPAT-induced attentional and vigilance impairments. Nefiracetam, another cognition enhancer, improved only the 8-OH-DPAT-induced impairments. Each compound tested alone had no effect on task performance. These results indicate that both serotonergic regulations, possibly via presynaptic 5-HT1A receptors and more likely via postsynaptic 5-HT2A receptors, lead similarly to attention deficits.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%