Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat

Lüttgen, Maria; Elvander, E.; Madjid, Nather; Ögren, Sven Ove

doi:10.1016/j.neuropharm.2005.01.007

Cited by 88 publications

(52 citation statements)

References 83 publications

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“…Thus, 5-HT 1A receptor antagonists fully blocked the 5-HT 1A receptor agonist-mediated impairments, thereby supporting the involvement of the 5-HT 1A receptor in the action of the agonists (Carli et al, 1995;Misane et al, 1998). In contrast, facilitated learning and memory have been observed after low, presumably presynaptic, doses of 8-OH-DPAT both in the PA task (Lü ttgen et al, 2005a) and in an operant-delayed matching to position task in the rat (Cole et al, 1994). Pretraining administration of 5-HT 1A receptor antagonists in rats has reported either facilitation (Sanger and Joly, 1989;Belcheva et al, 1997;Pitsikas et al, 2003), impairment (Cole et al, 1994), or no effects (Carli et al, 1997;Misane and Ö gren, 2003) on learning performance in various tasks.…”

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confidence: 62%

“…Because the effects of partial 5-HT 1A agonists on learning seem to depend on their relative efficacy at presynaptic versus postsynaptic 5-HT 1A receptors (Winsauer et al, 1999), the use of full 5-HT 1A receptor agonist, such as 8-OH-DPAT (Foreman et al, 1993), is critical for exploring the physiological role of 5-HT 1A receptors. Pretraining administration of 8-OH-DPAT (Sanger and Joly, 1989;Rowan et al, 1990;Carli et al, 1993;Misane and Ö gren, 2000;Lü ttgen et al, 2005a) impaired learning and memory performance in a dose-dependent manner in the passive avoidance (PA) task in the rat. 8-OH-DPAT also retarded spatial learning in the water maze (Carli et al, 1992;Kant et al, 1998) and radial maze tasks (Winter and Petti, 1987).…”

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confidence: 99%

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5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

Madjid

Tottie²,

Lüttgen³

et al. 2005

J Pharmacol Exp Ther

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The effects of 5-hydroxytryptamine 1A (5-HT 1A ) receptor ligands on aversive learning were examined in the passive avoidance (PA) task in mice. Anxiety and autonomic functions were investigated using the elevated plus-maze and heart rate measurements. The main findings from this study are as follows. 1) Pretraining administration of the 5-HT 1A receptor agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide] facilitated PA retention at low doses (0.01 and 0.03 mg/kg) but impaired PA retention at higher doses (0.1-1.0 mg/kg), consistent with previous findings in the rat. Serotonin (5-hydroxytryptamine; 5-HT) is a biogenic amine involved in a wide range of physiological functions, including learning and memory (Ö gren, 1985;Buhot et al., 2000). The ascending 5-HT neurons originating from the brainstem raphe nuclei innervate virtually all regions of the rat forebrain, allowing for widespread neuromodulatory actions (Dahlström and Fuxe, 1964) mediated by 14 identified receptor subtypes (Hoyer et al., 2002). Among the 5-HT receptor subtypes implicated in cognitive functions, the 5-HT 1A receptors are of special interest because they are abundant in brain

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confidence: 62%

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confidence: 99%

5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

Madjid

Tottie²,

Lüttgen³

et al. 2005

J Pharmacol Exp Ther

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“…41,42 Moreover, hippocampal 5-HT and 5-HT 1A receptors are important for emotional learning in the rat. 42,44 In this context, the finding of gender differences in 5-HT turnover in the St and Hp intriguing indicates the possibility for sexdependent control of the mood-related behavioral functions. Depression is a frequent comorbidity in schizophrenic patients with appearance to have changes in serotonergic transmission 43 probably related to some of the negative symptomatology seen in schizophrenia.…”

Section: Discussionmentioning

confidence: 93%

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

et al. 2007

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The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous ( þ /À) male and female mice expressing 35-40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 ( þ /À) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 ( þ /À) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 ( þ /À) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 ( þ /À) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurr1 mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.

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“…The differences in dose response in mediating behavioral performance after TBI may be due to alterations in the number of 5-HT 1A receptors, receptor sensitivity (Kreiss and Lucki, 1992), or effects at pre-synaptic versus post-synaptic receptors (Barnes and Sharp, 1999;Lü ttgen et al, 2005;Meneses, 2007). In addition to 5-HT 1A -receptor agonist properties, BUS is also a partial D 2 antagonist (Coop and McNaughton, 1991;McMillen et al, 1983), which could explain, in part, the worsening effect seen with the higher BUS dose, if it surpassed its threshold for 5-HT 1A -receptor activation and instead antagonized D 2 receptors.…”

Section: Discussionmentioning

confidence: 99%

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Olsen

Sozda

Cheng

et al. 2012

Journal of Neurotrauma

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The aim of this study was to evaluate the potential efficacy of the serotonin 1A (5-HT 1A ) receptor agonist buspirone (BUS) on behavioral and histological outcome after traumatic brain injury (TBI). Ninety-six isofluraneanesthetized adult male rats were randomized to receive either a controlled cortical impact or sham injury, and then assigned to six TBI and six sham groups receiving one of five doses of BUS (0.01, 0.05, 0.1, 0.3, or 0.5 mg/kg) or saline vehicle (VEH, 1.0 mL/kg). Treatments began 24 h after surgery and were administered intraperitoneally once daily for 3 weeks. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative days 1-5 and 14-19, respectively. Morphologically intact CA1/ CA3 cells and cortical lesion volume were quantified at 3 weeks. No differences were observed among the BUS and VEH sham groups in any end-point measure and thus the data were pooled. Regarding the TBI groups, repeated-measures ANOVAs revealed that the 0.3 mg/kg dose of BUS enhanced cognitive performance relative to VEH and the other BUS doses ( p < 0.05), but did not significantly impact motor function. Moreover, the same dose conferred selective histological protection as evidenced by smaller cortical lesions, but not greater CA1/ CA3 cell survival. No significant behavioral or histological differences were observed among the other BUS doses versus VEH. These data indicate that BUS has a narrow therapeutic dose response, and that 0.3 mg/kg is optimal for enhancing spatial learning and memory in this model of TBI. BUS may have potential as a novel pharmacotherapy for clinical TBI.

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Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat

Cited by 88 publications

References 83 publications

5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

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Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat

Cited by 88 publications

References 83 publications

5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

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Product

Resources

About

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone