Pharmacological alleviation of cholinergic lesion induced memory deficits in rats

Haroutunian, Vahram; Kanof, Philip D.; Davis, Kenneth L.

doi:10.1016/0024-3205(85)90531-4

Cited by 117 publications

(37 citation statements)

References 26 publications

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“…At higher doses, both drugs induced a significant and doserelated decrease in power of high-frequency bands, particularly of the 7.25-to 12-Hz band, which, however, was enhanced after lower doses of PHY. This diphasic effect has previously been reported in the same animal model [28] and in rats both in behavioral studies [34] and in hip- pocampal recordings of theta rhythm after injection of PHY and other cholinomimetic drugs [35,36]. Although in this study EEG was recorded using epidural electrodes which are located above the hippocampus, we can presume that we recorded not only neocortical electric signals but also spectral components generated in the limbic circuits and diffused to the cortical layers, similar to rats [37].…”

Section: Discussionmentioning

confidence: 86%

Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse

Tebano

Luzi²,

Palazzesi³

et al. 1999

Neuropsychobiology

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The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.05, 0.1, 0.2 mg/kg) and heptylphysostigmine (HEP; 0.5, 2, 6 mg/kg) on electroencephalographic (EEG) activity and flash visual evoked potentials (f-VEP) in the occipital cortex were compared in DBA/2 mice. EEG spectral analysis of awake periods showed that PHY at all doses and HEP at 2 mg/kg induced an increase of power in the 4.25- to 7-Hz frequency band. Furthermore, PHY at the higher doses and HEP at all doses induced a decrease of power in the 7.25- to 12-Hz frequency band, while the lower doses of PHY (0.01, 0.025 mg/kg) produced an increase of this band. EEG effects elicited by the two drugs were similar, when doses displaying analogous biochemical effects (acetylcholinesterase inhibition) were used (i.e. 0.01 and 0.025 mg/kg of PHY versus 0.5 and 2 mg/kg of HEP). PHY and HEP induced similar changes in f-VEPs. Amplitudes of early and late components (P1N1, N1P2, P4N4 and particularly N1P3) were enhanced, while amplitudes of middle components were depressed after all doses. The peak latency measures were generally delayed, even though, after the lower doses, a trend to a latency reduction was evident in late components. This finding might indicate a possible effect on stimulus speed diffusion by ‘low therapeutic’ doses, analogous to the ones used in men. Our data show that both drugs are effective in modifying EEG and f-VEP parameters connected with brain cholinergic function, although in a very narrow dose range.

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Section: Discussionmentioning

confidence: 86%

Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse

Tebano

Luzi²,

Palazzesi³

et al. 1999

Neuropsychobiology

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“…In aged rhesus monkeys, the aadrenergic agonists clonidine [5] and guanfacine [6] have been shown to improve performance on a delayed re sponse task that tests spacial working memory. In AD, however, monotherapy with clonidine has not resulted in clinically significant cognitive improvement [7].It has been shown that nucleus-basalis-lesioned rats show performance deficits that are reversed by treatment with the acetylcholinesterase inhibitor physostigmine [8], When these animals are given additional lesions of the Accepted: December 2. 1993 ascending noradrenergic bundle, the performance deficit is unchanged in magnitude but is no longer reversed by physostigmine.…”

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confidence: 99%

A Pilot Study of Clonidine Plus Physostigmine in Alzheimer's Disease

Bierer¹,

Aisen²,

Davidson³

et al. 1994

Dement Geriatr Cogn Disord

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To assess the feasibility of one approach to combined cholinergic/noradrenergic treatment in Alzheimer's disease, ten patients were enrolled in a 2-week placebo-controlled study of oral physostigmine plus clonidine. The Alzheimer's Disease Assessment Scale (ADAS) was used as the primary outcome measure. Neither physostigmine alone, nor the combination of physostigmine plus clonidine, was associated with a statistically significant improvement for the group. Three patients did show an improvement of at least 4 points on the total ADAS score with the drug combination. The implications of these results for treatment strategies are discussed.

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“…In keeping with a 'combined-lesion' strategy, the present study examined the effects of serotonergic depletion (via induced presynaptic release) on memory in hypocholinergic animals. Using nbM-lesioned rats trained on passive avoidance, the specific aims of the present study were to determine whether p-chloroamphetamine, a known serotonergic releasing/depleting agent [25][26][27] would (1) further impair retention performance, and (2) block the often reported memory-enhancing effect of physostigmine [28][29][30][31].…”

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confidence: 99%

Serotonergic Modulation of Cholinergic Systems Involved in Learning and Memory in Rats

Santucci¹,

Kanof²,

Haroutunian³

1990

Dement Geriatr Cogn Disord

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Rats received either N-methyl-D-aspartic-acid-induced bilateral lesions (50 nmol/l µl/side) of a major forebrain cholinergic nucleus (nucleus basalis of Meynert, nbM) or sham operations. After an approximate 1-month recovery period, all subjects were trained and tested on a one-trial passive avoidance task. Thirty minutes prior to training, half of the subjects in each surgical condition were injected with the serotonergic releasing/depleting agent p-chloroamphetamine (2.5 mg/kg), while the other half of subjects received saline injections. Immediately after training, half of the p-chloroamphetamine-injected and saline-injected subjects in each surgical condition were injected with the cholinesterase inhibitor physostigmine (0.06 mg/kg), while the other half were injected with saline. All animals were tested for retention 72 h following training. Disruption of test performance was seen in (1) saline-injected nbM-lesioned animals; (2) sham animals treated with physostigmine alone, and (3) sham and nbM-lesioned animals treated with either p-chloroamphetamine alone, or with p-chloroamphetamine plus physostigmine. Only nbM-lesioned subjects injected with physostigmine alone exhibited enhanced test performance. Lesions of the nbM produced stern depletions in cortical cholinergic enzyme markers (choline acetyltransferase, CAT, and acetylcholinesterase, AChE). Interestingly, p-chloroamphetamine exaggerated both the CAT and AChE depletions in nbM-lesioned animals. These data were interpreted as providing further evidence in support of the view that the cholinergic and serotonergic systems interact at a cognitive and at a neurochemical level. Implications for the therapeutics of Alzheimer''s disease are discussed.

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Pharmacological alleviation of cholinergic lesion induced memory deficits in rats

Cited by 117 publications

References 26 publications

Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse

Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse

A Pilot Study of Clonidine Plus Physostigmine in Alzheimer's Disease

Serotonergic Modulation of Cholinergic Systems Involved in Learning and Memory in Rats

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