Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased

Ruitenbeek, Peter van; Vermeeren, Annemiek; Riedel, Wim J.

doi:10.1016/j.euroneuro.2009.12.003

Cited by 12 publications

(12 citation statements)

References 60 publications

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“…Given the lack of memory-enhancing effects on short-term memory in young mice, these data suggest that a significant increase in the latency to step down revealed in 7-month-old mice treated with dimebon during the first recall session was due to its non-specific inhibitory effects on locomotion. Data on the suppressive effects of dimebon on exploratory vertical activity in the novel cage are in line with the well-documented sedative effects of histamine receptor blockers (Passani et al, 2007;Van Ruitenbeek et Step down avoidance 3-m-o 0.1 mg/kg --0.5 mg/kg + -7-m-o 0.5 mg/kg + + n.a. n.a.…”

Section: Discussionsupporting

confidence: 71%

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Vignisse

Steinbusch

Bolkunov

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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a b s t r a c t a r t i c l e i n f oPre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice.

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Section: Discussionsupporting

confidence: 71%

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Vignisse

Steinbusch

Bolkunov

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…(2008) also found a mean increase in memory scanning speed after the administration of dexchlorpheniramine 4 mg, but the difference failed to reach significance. The lack of effects of cetirizine on word learning and recall is also in line with results from previous studies that failing to find significant effects of first generation antihistamines on performance in similar word learning tests (Turner et al ., 2006; van Ruitenbeek et al ., 2008; 2010). The differential effects of antihistamines on performance in memory scanning and word learning tasks may be due to differences in the degree to which they involve speeded information processing.…”

Section: Discussionmentioning

confidence: 99%

Histamine H₁ receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory

Ruitenbeek

Vermeeren

Riedel

2010

British J Pharmacology

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The histaminergic neurotransmitter system is currently under investigation as a target for drug treatment of cognitive deficits in clinical disorders. The therapeutic potential of new drugs may initially be screened using a model of histaminergic dysfunction, for example, as associated with the use of centrally active antihistamines. Of the selective second generation antihistamines, cetirizine has been found to have central nervous system effects. The aim of the present study was to determine whether cetirizine can be used as a tool to model cognitive deficits associated with histaminergic hypofunction. EXPERIMENTAL APPROACHThe study was conducted according to a three-way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed. KEY RESULTSCetirizine 10 mg impaired tracking performance and both doses impaired memory scanning speed. None of the other measures indicated impaired performance. CONCLUSION AND IMPLICATIONSCetirizine affects information processing speed, but these effects were not sufficient to serve as a model for cognitive deficits in clinical disorders.

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“…Because lorazepam causes sedation in addition to reducing anxiety (e.g., Van Ruitenbeek et al, 2010), a demonstration that the lorazepam effect on response choices in moral personal dilemmas was not a side effect of sedation was required. Table 1 shows that decision times contained a large degree of variation, especially as the lorazepam dose increased.…”

Section: Drug Effects On Dilemma Decision Timesmentioning

confidence: 99%

“…Indirect evidence points to an inhibitory role for negative emotion. For example, Valdesolo and DeSteno (2006) found that experimentally increasing mirth-related positive affect in participants increased their tendency to endorse harmful acts in moralpersonal dilemmas, implying that negative emotion should conversely play an inhibitory role in such acts. Similarly, a single 30-mg dose of citalopram (a selective serotonin reuptake inhibitor drug that is used to treat a wide range of affective illnesses, including anxiety disorders; Wade, Lepola, Koponen, Pedersen, & Pedersen, 1997) decreased the likelihood that participants would endorse harmful acts in moral-personal dilemmas (Crockett, Clark, Hauser, & Robbins, 2010).…”

mentioning

confidence: 99%

A dose of ruthlessness: Interpersonal moral judgment is hardened by the anti-anxiety drug lorazepam.

Perkins¹,

Leonard²,

Weaver³

et al. 2013

Journal of Experimental Psychology: General

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Neuroimaging data suggest that emotional brain systems are more strongly engaged by moral dilemmas in which innocent people are directly harmed than by dilemmas in which harm is remotely inflicted. In order to test the possibility that this emotional engagement involves anxiety, we investigated the effects of 1 mg and 2 mg of the anti-anxiety drug lorazepam on the response choices of 40 healthy volunteers (20 male) in moral-personal, moral-impersonal, and nonmoral dilemmas. We found that lorazepam caused a dose-dependent increase in participants' willingness to endorse responses that directly harm other humans in moral-personal dilemmas but did not significantly affect response choices in moral-impersonal dilemmas or nonmoral dilemmas. Within the set of moral-personal dilemmas that we administered, lorazepam increased the willingness to harm others in dilemmas where harm was inflicted for selfish reasons (dubbed low-conflict dilemmas) as well as responses to dilemmas where others were harmed for utilitarian reasons (i.e., for the greater good, dubbed high-conflict dilemmas). This suggests that anxiety exerts a general inhibitory effect on harmful acts toward other humans regardless of whether the motivation for those harmful acts is selfish or utilitarian. Lorazepam is also a sedative drug, but we found that lorazepam slowed decision times equally in all 3 dilemma types. This finding implies that its specific capacity to increase ruthlessness in moral-personal dilemmas was not a confound caused by sedation.

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Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased

Cited by 12 publications

References 60 publications

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Histamine H₁ receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory

A dose of ruthlessness: Interpersonal moral judgment is hardened by the anti-anxiety drug lorazepam.

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Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased

Cited by 12 publications

References 60 publications

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory

A dose of ruthlessness: Interpersonal moral judgment is hardened by the anti-anxiety drug lorazepam.

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Histamine H₁ receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory