Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats

Jeltsch, Hélène; Bertrand, Fabrice; Galani, Rodrigue; Lazarus, Christine; Schimchowitsch, Sarah; Cassel, Jean‐Christophe

doi:10.1007/s00213-004-1783-0

Cited by 34 publications

(22 citation statements)

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“…Working memory procedure: During nine other consecutive days, the platform was placed in a new location each day, and the rats were released from each of two starting points on two consecutive trials separated by 10 s. The platform locations were those described by Jeltsch et al (2004a).…”

Section: Behavioral Testingmentioning

confidence: 99%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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In Alzheimer's disease (AD), cognitive decline is linked to cholinergic dysfunctions in the basal forebrain (BF), although the earliest neuronal damage is described in the entorhinal cortex (EC). In rats, selective cholinergic BF lesions or fiber-sparing EC lesions may induce memory deficits, but most often of weak magnitude. This study investigated, in adult rats, the effects on activity and memory of both lesions, alone or in combination, using 192 IgG-saporin (OX7-saporin as a control) and L-N-methyl-D-aspartate to destroy BF and EC neurons, respectively. Rats were tested for locomotor activity in their home cage and for working-and/or reference-memory in various tasks (water maze, Hebb-Williams maze, radial maze). Only rats with combined lesions showed diurnal and nocturnal hyperactivity. EC lesions impaired working memory and induced anterograde memory deficits in almost all tasks. Lesions of BF cholinergic neurons induced more limited deficits: reference memory was impaired in the probe trial of the water-maze task and in the radial maze. When both lesions were combined, performance never improved in the water maze and the number of errors in the Hebb-Williams and the radial mazes was always larger than in any other group. These results (i) indicate synergistic implications of BF and EC in memory function, (ii) suggest that combined BF cholinergic and fiber-sparing EC lesions may model aspects of anterograde memory deficits and restlessness as seen in AD, (iii) challenge the cholinergic hypothesis of cognitive dysfunctions in AD, and (iv) contribute to open theoretical views on AD-related memory dysfunctions going beyond the latter hypothesis.

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Section: Behavioral Testingmentioning

confidence: 99%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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“…on day 5. This indicates that their results probably relates to effects on working or short-term memory functions, which has shown to be impaired by intraseptal injections of 8-OH-DPAT (0.5 and 4 lg) (Jeltsch et al, 2004). In view of the short retention time used by Bertrand et al (2000), it seems likely that 8-OH-DPAT is still bound to brain 5-HT 1A receptors during retention testing, since the half-life of 8-OH-DPAT in the rat brain is 40 min (Yu and Lewander, 1997).…”

Section: Discussionmentioning

confidence: 92%

“…The present experiment was conducted with the more active enantiomer, (R)-(1)-8-hydroxy-2-(di-npropylamino)tertralin hydrobromide ((R)-8-OH-DPAT) (SigmaAldrich, Stockholm, Sweden), which, unlike the racemic form, is a full agonist at the 5-HT 1A receptor (Cornfield et al, 1991). The doses of (R)-8-OH-DPAT (1 and 4 lg) were based on earlier studies in the rat where intraseptal infusions of 8-OH-DPAT (4 lg) was reported to impair water maze performance (Bertrand et al, 2000;Jeltsch et al, 2004;Koenig et al, 2008). D-(2)-2-amino-5-phosphonopentanoic acid (D-AP5) (Tocris, Bromma, Sweden) is the active enantiomer of AP5 and a competitive antagonist on the glutamatergic NMDA receptors (Davies and Watkins, 1982).…”

Section: Drugsmentioning

confidence: 99%

“…In one study, intraseptal 8-OH-DPAT (0.5 and 4 lg) was reported to slightly impair water maze acquisition, suggested to be due to a reduction in hippocampal cholinergic tonus or indirectly via an effect on anxiety (Bertrand et al, 2000). Another study showed that intraseptal 8-OH-DPAT impaired working memory performance, which was attributed to a nonspecific ''global cognitive deficiency'' (Jeltsch et al, 2004) and a recent study showed impaired spatial reference memory following intraseptal 8-OH-DPAT infusion (Koenig et al, 2008). In contrast to these studies in rats, intraseptal 8-OH-DPAT (1 lg) facilitated acquisition in a spatial discrimination task in mice (Micheau and Van Marrewijk, 1999).…”

Section: Introductionmentioning

confidence: 96%

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5‐HT_1A and NMDA receptors interact in the rat medial septum and modulate hippocampal‐dependent spatial learning

et al. 2009

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Cholinergic and GABAergic neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) projecting to the hippocampus, constitute the septohippocampal projection, which is important for hippocampal-dependent learning and memory. There is also evidence for an extrinsic as well as an intrinsic glutamatergic network within the MS/vDB. GABAergic and cholinergic septohippocampal neurons express the serotonergic 5-HT(1A) receptor and most likely also glutamatergic NMDA receptors. The aim of the present study was to examine whether septal 5-HT(1A) receptors are important for hippocampal-dependent long-term memory and whether these receptors interact with glutamatergic NMDA receptor transmission in a manner important for hippocampal-dependent spatial memory. Intraseptal infusion of the 5-HT(1A) receptor agonist (R)-8-OH-DPAT (1 or 4 microg/rat) did not affect spatial learning in the water maze task but impaired emotional memory in the passive avoidance task at the higher dose tested (4 microg/rat). While intraseptal administration of (R)-8-OH-DPAT (4 microg) combined with a subthreshold dose of the NMDA receptor antagonist D-AP5 (1 microg) only marginally affected spatial acquisition, it produced a profound impairment in spatial memory. In conclusion, septal 5-HT(1A) receptors appears to play a more prominent role in emotional than in spatial memory. Importantly, septal 5-HT(1A) and NMDA receptors appear to interact in a manner, which is particularly critical for the expression or retrieval of hippocampal-dependent long-term spatial memory. It is proposed that NMDA receptor hypofunction in the septal area may unmask a negative effect of 5-HT(1A) receptor activation on memory, which may be clinically relevant.

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“…Although the passive avoidance test was used here and in other studies [43,45,47,50,51] as a simple learning and memory task, other studies have used it as an index of attentional and emotional factors [9,20,36,40].…”

Section: Behavioral Testingmentioning

confidence: 99%

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

2005

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Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 F 10%) and significantly prolonged acquisition (398 F 62 s) and shortened retention (79 F 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 F 8%), they performed significantly better in the passive avoidance task (255 F 36 s and 145 F 18 s in acquisition and retention) than the vehicletreated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSFtreated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task. Published by Elsevier B.V.Theme: Disorders of the nervous system Topic: Ischemia

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Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats

Cited by 34 publications

References 58 publications

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

5‐HT_1A and NMDA receptors interact in the rat medial septum and modulate hippocampal‐dependent spatial learning

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

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Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats

Cited by 34 publications

References 58 publications

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

5‐HT1A and NMDA receptors interact in the rat medial septum and modulate hippocampal‐dependent spatial learning

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

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5‐HT_1A and NMDA receptors interact in the rat medial septum and modulate hippocampal‐dependent spatial learning