AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors

Kampen, M. Van; Selbach, Karin; Schneider, Renate; Schiegel, Elleonore; Boess, Frank; Schreiber, Rudy

doi:10.1007/s00213-003-1668-7

Cited by 158 publications

(97 citation statements)

References 43 publications

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“…The a7 nicotinic receptor is expressed in high concentration in the hippocampus. The a7 agonist, ARR 17779, enhanced working memory and social recognition (Van Kampen et al, 2004) in rodent models. Further, infusion into the hippocampus of dihydro-b-erythroidine, a selective a4b2 antagonist, and methyllycaconitine, a selective a7 antagonist, produced working memory impairments (Felix and Levin, 1997).…”

Section: Introductionmentioning

confidence: 95%

Dose-Related Enhancement of Mood and Cognition in Smokers Administered Nicotine Nasal Spray

Myers

Taylor

Moolchan

et al. 2007

Neuropsychopharmacol

125

126

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The discovery of the role of nicotinic receptors in attention and memory has led to the testing of nicotinic analogs as cognitive enhancing agents in patient populations. Empirical information about nicotine's ability to enhance elements of attention and memory in normal individuals might guide development of therapeutic uses of nicotine in cognitively impaired populations. The purpose of this study was to determine the effect of nicotine on continuous attention, working memory, and computational processing in tobacco-deprived and nondeprived smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind, placebo-controlled, within-subject study, in which they were overnight (12 h) tobacco deprived at one session and smoked ad libitum before the other session. At each session, participants received 0, 1, and 2 mg nicotine via nasal spray in random order at 90 min intervals. Before and after each dose, a battery of cognitive, subjective, and physiological measures was administered, and blood samples were taken for plasma nicotine concentration. Overnight tobacco deprivation resulted in impaired functioning on all cognitive tests and increased self-reports of tobacco craving and negative mood; nicotine normalized these deficits. In the nondeprived condition, nicotine enhanced performance on the continuous performance test (CPT) and an arithmetic test in a dose-related manner, but had no effect on working memory. In general, women were more sensitive than men to the subjective effects of nicotine. These results provide an unequivocal determination that nicotine enhanced attentional and computational abilities in nondeprived smokers and suggest these cognitive domains as substrates for novel therapeutic indications.

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Section: Introductionmentioning

confidence: 95%

Dose-Related Enhancement of Mood and Cognition in Smokers Administered Nicotine Nasal Spray

Myers

Taylor

Moolchan

et al. 2007

Neuropsychopharmacol

125

126

View full text Add to dashboard Cite

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“…Reduction in forebrain NMDA receptors has been reported in TM-NRG1 mutants (Stefansson et al, 2002) and abnormalities in social behaviour have been reported in hypomorphic NMDA mutants (Mohn et al, 1999;Duncan et al, 2004); however, these studies did not resolve sociability vs social novelty. There is also evidence for α7 nicotinic acetylcholine receptor [α7nAChR] dysregulation in schizophrenia (Leonard and Freeman, 2006;Olincy et al, 2006), for NRG1 modulation of α7nAChR currents (Chang and Fischbach, 2006) and for the involvement of the α7nAChR in social recognition (van Kampen et al, 2004). Regarding the long-standing dopamine [DA] hyperfunction hypothesis of schizophrenia (Kapur et al, 2005;Seeman et al, 2006), NRG1 can regulate aspects of DAergic neurotransmission (Yurek et al, 2004) and DAergic dysfunction, particularly in the medial prefrontal cortex, has been implicated in the detection of salient social and non-social stimuli (O'Tuathaigh et al, 2003;Bassareo et al, 2002;De Leonibus et al, 2006).…”

Section: Nrg1 and Schizophreniamentioning

confidence: 99%

Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin 1

et al. 2007

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“…a7 agonists have been shown to improve performance in various cognitive tasks in rodents, including one-way active avoidance, 8 or 17-arm radial maze, Morris water maze, object recognition and social recognition (Arendash et al, 1995;Hashimoto et al, 2008;Kem, 2000;Levin et al, 1999;Pichat et al, 2007;Timmermann et al, 2007;Van Kampen et al, 2004;Wishka et al, 2006). The dual effect of SSR180711 exerted on disrupted and persistent LI is particularly remarkable in that in terms of effects on performance, the drug influenced the pre-exposed MK801 and neonatal L-NoArg groups in opposite direction from that of the pre-exposed amphetamine group, namely, improved conditioning in the former and impaired conditioning in the latter.…”

Section: Ssr180711-behavioral and Psychological Profilementioning

confidence: 99%

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Barak

Arad

Levie

et al. 2009

Neuropsychopharmacol

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Schizophrenia symptoms can be segregated into positive, negative and cognitive, which exhibit differential sensitivity to drug treatments. Accumulating evidence points to efficacy of a7 nicotinic receptor (nAChR) agonists for cognitive deficits in schizophrenia but their activity against positive symptoms is thought to be minimal. The present study examined potential pro-cognitive and antipsychotic activity of the novel selective a7 nAChR partial agonist SSR180711 using the latent inhibition (LI) model. LI is the reduced efficacy of a previously nonreinforced stimulus to gain behavioral control when paired with reinforcement, compared with a novel stimulus. Here, no-drug controls displayed LI if non-reinforced pre-exposure to a tone was followed by weak but not strong conditioning (2 vs 5 tone-shock pairings). MK801 (0.05 mg/kg, i.p.) -treated rats as well as rats neonatally treated with nitric oxide synthase inhibitor L-NoArg (10 mg/kg, s.c.) on postnatal days 4-5, persisted in displaying LI with strong conditioning, whereas amphetamine (1 mg/kg) -treated rats failed to show LI with weak conditioning. SSR180711 (0.3, 1, 3 mg/kg, i.p.) was able to alleviate abnormally persistent LI produced by acute MK801 and neonatal L-NoArg; these models are believed to model cognitive aspects of schizophrenia and activity here was consistent with previous findings with a7-nAChR agonists. In addition, unexpectedly, SSR180711 (1, 3 mg/kg, i.p.) potentiated LI with strong conditioning in nodrug controls and reversed amphetamine-induced LI disruption, two effects considered predictive of activity against positive symptoms of schizophrenia. These findings suggest that SSR180711 may be beneficial not only for the treatment of cognitive symptoms in schizophrenia, as reported multiple times previously, but also positive symptoms.

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AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors

Abstract: AR-R17779 increased social recognition memory by activation of alpha(7)-nAChRs, suggesting that alpha(7)-nAChR agonists possess cognitive-enhancing properties.

Cited by 158 publications

References 43 publications

Dose-Related Enhancement of Mood and Cognition in Smokers Administered Nicotine Nasal Spray

Dose-Related Enhancement of Mood and Cognition in Smokers Administered Nicotine Nasal Spray

Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin 1

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

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