Within-subject memory decline in middle-aged rats: effects of intraseptal tacrine

Sabolek, Helen R.; Bunce, Jamie G.; Giuliana, Derek J.; Chrobak, James J.

doi:10.1016/j.neurobiolaging.2003.12.006

Cited by 14 publications

(17 citation statements)

References 43 publications

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“…However, in normal rats these drugs may increase signal capacity within the septohippocampal pathway transforming hippocampal theta activity into an epileptiform that adversely affects behavior (Sabolek et al, 2004b; Wallenstein and Hasselmo, 1997). Evidence from a number of preparations suggests that there is a restricted range of acetylcholine levels in the medial septum and hippocampus that optimizes cognitive functions (Hasselmo, 2006; Roland et al, 2008; Sabolek et al, 2004a).…”

Section: Discussionmentioning

confidence: 99%

“…For example, intraseptal infusion of tacrine, at doses of 2.5 and 12.5 μg, has been shown to increase memory performance in cognitively impaired young rats (Sabolek et al, 2004a), but impair performance in aged (Sabolek et al, 2004b) and normal adult rats (Sabolek et al, 2005). Given past research with tacrine and related drugs, it appears that cholinergic manipulations of the medial septum/diagonal band may depend on the interaction of several factors, including brain integrity, cognitive status and the task used for behavioral assessment.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of systemic and intraseptal administration of the acetylcholinesterase inhibitor tacrine on the recovery of spatial behavior in an animal model of diencephalic amnesia

Roland

Levinson

Vetreno

et al. 2010

European Journal of Pharmacology

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Several lines of evidence suggest that acetylcholinesterase inhibitors (AChE) inhibitors have their cognitive enhancing effects by stimulating cholinergic receptors within the medial septum. However, intraseptal administration of cholinergic enhancing drugs produce mixed results that appear to depend on both the integrity of the medial septum as well as task demands. Three experiments were conducted to determine the relationship between increased cholinergic activity within the medial septum and hippocampus and behavioral recovery in a model of diencephalic amnesia produced by pyrithiamine-induced thiamine deficiency (PTD). In Experiment 1, systemic tacrine (0.0, 0.75, 1.5 mg/kg) was administered to PTD and pair-fed (PF) rats prior to a spontaneous alternation task. Without tacrine, PF rats alternated at a higher rate than PTD rats. Both doses of tacrine increased alternation in PTD rats to within the range of PF rats. In Experiment 2, three doses of intraseptal tacrine (2.5, 5.0, 12.5 μg) were administered to PTD and PF rats and changes in hippocampal acetylcholine efflux were assessed. Both the 5.0 and 12.5 μg doses significantly increased hippocampal acetylcholine levels, but the change was greater in the PTD rats. In Experiment 3, despite the fact that both intraseptal doses of tacrine (5.0, 12.5 μg) increased hippocampal acetylcholine levels, only 5.0 μg significantly improved alternation scores in PTD rats. Thus, when there is basal forebrain cholinergic cell loss in conjunction with diencephalic pathology, the therapeutic range of AChE-I in the medial septum and the effective doses do not directly map onto changes in acetylcholine efflux in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential effects of systemic and intraseptal administration of the acetylcholinesterase inhibitor tacrine on the recovery of spatial behavior in an animal model of diencephalic amnesia

Roland

Levinson

Vetreno

et al. 2010

European Journal of Pharmacology

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“…Furthermore, many of these tasks suggest sex differences in the extent or the onset of cognitive decline. A short list of tasks would include olfactory memory (Roman et al, 1996; Taylor et al, 1999), contextual memory during fear conditioning (Kaczorowski and Disterhoft, 2009; Moyer and Brown, 2006), spatial working memory examined on the radial arm maze (Dellu-Hagedorn et al, 2004; Granholm et al, 2008; Sabolek et al, 2004) however see (Dellu et al, 1997; Jacobson et al, 2008; Oler and Markus, 1998), performance on various spatial mazes (Fouquet et al, 2009; Ingram, 1988; Kametani et al, 1989), and retention of inhibitory/passive avoidance (Benice et al, 2006; Moretti et al, 2011; Paris et al, 2010; Samorajski et al, 1985). Tests that examine recognition of novel objects or object locations have reported mixed results (Benice et al, 2006; Blalock et al, 2003; Fahlstrom et al, 2009; Paris et al, 2010), possibly due to procedures that render the task more or less hippocampal-dependent (Broadbent et al, 2009; Hammond et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

Foster

2012

Progress in Neurobiology

147

157

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In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D-aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate-term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging.

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“…In addition, impairments may be more consistent with repeated testing such that within-subject impaired or unimpaired performance is maintained across multiple testing sessions (Sabolek et al, 2004). However, little is known concerning the reliability of episodic spatial memory deficits following repeated testing on the water maze.…”

Section: Introductionmentioning

confidence: 99%

Assessing the emergence and reliability of cognitive decline over the life span in Fisher 344 rats using the spatial water maze

Guidi

Kumar

Rani

et al. 2014

Front. Aging Neurosci.

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The spatial water maze is routinely used to investigate hippocampal-dependent spatial memory and the biological mechanisms that underlie variability in cognitive decline during aging. The utility of the task for repeated testing in order to examine the trajectory of cognitive decline and to prescreen animals prior to therapeutic interventions maybe limited due to carryover effects of repeated training. The current study examines the role of carryover effects, as well as the reliability of individual differences, in determining age-related impairment on episodic and reference memory versions of the water maze task. Results indicate that impaired acquisition of episodic spatial information emerges in middle-age and the propensity for impairment increases with advancing age. While learning was variable across animals, acquisition deficits for episodic information were reliable across training sessions in middle-age and aged rats. A significant impairment in the 24~h retention of episodic spatial information was observed in aged animals. When animals were trained to the same location (i.e., reference memory), an impairment was limited to the rate of acquisition in aged animals. However, with continued training, all aged animals were able to acquire a reference memory and no age differences were observed in the 24~h retention of a spatial reference memory. Together, the results point to a progressive impairment in episodic spatial memory with advancing age and suggest that tests of episodic spatial memory are reliable and more sensitive than reference memory for detecting cognitive decline.

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Within-subject memory decline in middle-aged rats: effects of intraseptal tacrine

Cited by 14 publications

References 43 publications

Differential effects of systemic and intraseptal administration of the acetylcholinesterase inhibitor tacrine on the recovery of spatial behavior in an animal model of diencephalic amnesia

Differential effects of systemic and intraseptal administration of the acetylcholinesterase inhibitor tacrine on the recovery of spatial behavior in an animal model of diencephalic amnesia

Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

Assessing the emergence and reliability of cognitive decline over the life span in Fisher 344 rats using the spatial water maze

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