Learning and memory deficits after lesions of the nucleus basalis magnocellularis: Reversal by physostigmine

Murray, Candice; Fibiger, Hans C.

doi:10.1016/0306-4522(85)90273-8

Cited by 302 publications

(110 citation statements)

References 21 publications

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“…1988;Riekkinen et al, 1990). These deficits are sirnilar to those seen after administration of the central muscarinic receptor antaçonist atropine sulfate (Whishaw et al,l985), and can be reversed with the muscarinic receptor agonist pilocarpine or the AChE irkibitor 192 IgG-Saporin in Neonatal Rats 4 physostigmine (Murray & Fibiger, 1985;Murray & Fibiger, 1986;Dokla & Thal, 1988). Since hippocampal ChAT activity was unaffected in al1 of these studies, the cortical cholinergic projection frorn the nucleus basalis area was initially thought to be a requisite component of intact spatiaI and nonspatial memory systems,…”

Section: E~pct-in~ Rilially H ~H C E J Cholïm~-gic D E F I C ï~-Ex-cmentioning

confidence: 90%

“…Since the loss of cholinergic projections to 192 IgG-Saporin in Neonatal Rats 3 the hippocampus and cortex and the loss of cholinergic ce11 bodies in the nucleus basalis of Meynert are thought to underlie some of the major cognitive deficits in Alzheimer's disease, animal modeis were designed to disrupt the functional integnty ofbasal forebrain connections in adulthood, either pharmacologically (excitotoxins) or mechanicaily (electrolytic or transection lesions). Indeed, it was subsequently demonstrated that basal forebrain cholinergic lesions did produce marked behavioral impairments on tasks involving leaming and rnernory components, such as the Morris water maze and the radial a m maze (Hepler, Wenk, Cribbs, Olton & Coyle, 1985;Murray & Fibiger, 1985;Dokla & Thal, 1988;Riekkinen, Sirvio & Riekkinen, 1990). Nevertheless, the iesion studies outlined below contain method-dependent inconsistencies which have cast doubt on the involvement of the cholinergic basal forebrain in learning and rnemory pei-se.…”

Section: E~pct-in~ Rilially H ~H C E J Cholïm~-gic D E F I C ï~-Ex-cmentioning

confidence: 99%

“…Specifically, rodent memory processes can be facilitated or irnpeded by cholinergic agonists or antagonists respectively (Murray & Fibiger, 1985;Whishaw, O'Connor & Dunnett, 1985;Murray & Fibiger, 1986). In addition, age-related deficits in rodent mnemonic abiIities have been associated with concomitant reductions in cortical and hippccampal choline acetyltransferase (ChAT) activity, acetylcholinesterase (AChE) fiber density and hippocampal muscarinic receptor numbers (Lippa, Pelham, Beer, Critchett, Dean & Bartus, 1980;Strong, Hicks, Hsu, Bartus & Enna, 1980).…”

Section: Introductmnmentioning

confidence: 99%

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Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects?

Sherren

Pappas

Fortin

1999

Developmental Brain Research

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Section: E~pct-in~ Rilially H ~H C E J Cholïm~-gic D E F I C ï~-Ex-cmentioning

confidence: 90%

Section: E~pct-in~ Rilially H ~H C E J Cholïm~-gic D E F I C ï~-Ex-cmentioning

confidence: 99%

Section: Introductmnmentioning

confidence: 99%

See 1 more Smart Citation

Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects?

Sherren

Pappas

Fortin

1999

Developmental Brain Research

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“…THA treatment increases glucose utilization in AD patients in cortical (frontal and temporal corti ces) and subcortical areas (Nordberg et aI., 1992;Nordberg, 1993). PHY and THA improve memory deficits in nucleus basalis-Iesioned rats (Murray and Fibiger, 1985;K wo-On-Yuen et aI., 1990) and in memory-impaired aged monkeys (Bartus and Dean, 1988). It would be interesting to know if LCGU is modified in parallel with behavioral im provement in these animals.…”

Section: Resultsmentioning

confidence: 99%

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Bassant

Jazat-Poindessous

Lamour

1995

J Cereb Blood Flow Metab

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Summary: The effects of the centrally acting anti cholinesterases tacrine (tetrahydroaminoacridine, THA) and physostigmine (PHY), on local cerebral glucose uti lization (LCGU) have been studied in 27-month-old rats, using the autoradiographic e4Cjdeoxyglucose technique. THA (10 mg/kg i.p.) increased LCGU significantly in 13 of the 54 regions studied (24%) including insular, parietal, temporal, and retrosplenial cortices, septohippocampal system, thalamus, lateral habenula, and superior collicu Ius. In these regions, the average THA-induced increase in LCGU was 24% above control. The whole brain mean LCGU was not significantly increased. PHY (0. 5 mg/kg) increased LCGU in 18% of the regions (average eleva tion, 23%). The whole brain mean LCGU increased byThe centrally acting cholinesterase inhibitor tet rahydroaminoacridine (THA, tacrine) has been re ported to improve cognitive deficits in subpopula tions of Alzheimer's disease (AD) patients. Several multicenter studies (Eagger et aI., 1991; Davis et aI. , 1992; Farlow et aI., 1992; Knapp et aI., 1994) have confirmed the initial positive results of Sum mers (S ummers et aI., 1986). The effects of THA in mildly demented AD patients persist during long term treatment and indicate that THA might not only act on symptoms but also delay the disease process (Nordberg et aI., 1992). The mechanisms mediating the effects of THA are far from clear, but experimental data indicate that THA may produce its therapeutic effects, at least in part, via its action on cholinergic transmission (for review, see Free man and Dawson, 1991). In experimental animals, 1093 7% (p < 0.05). The regional distributions of THA-and PHY-induced increases in LCGU were extremely similar and overlapped the distribution of the M2 muscarinic re ceptors and that of acetylcholinesterase activity, suggest ing that the major effects of THA and PHY on LCGU result from their anticholinesterase action. As compared to those of 3-month-old rats, both the number of regions affected and the amplitude of the metabolic activation were significantly less in aged rats. However, the drugs were still active in old rats and compensated for the age related hypometabolism in some brain areas.

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“…Preliminary observations in one patient show that THA in creases glucose utilization in cerebral cortex and a few other structures (Nordberg et al, 1992). Phy sostigmine and THA improve memory deficits in nucleus basalis-Iesioned rats (Murray and Fibiger, 1985;Kwo-On-Yuen et al, 1990) and in memory impaired aged monkeys (Bartus and Dean, 1988). It would be interesting to know whether LeGU is modified in parallel with behavioral improvement in these animals.…”

Section: Effects Of Physostigminementioning

confidence: 99%

Tetrahydroaminoacridine and Physostigmine Increase Cerebral Glucose Utilization in Specific Cortical and Subcortical Regions in the Rat

Bassant

Jazat

Lamour

1993

J Cereb Blood Flow Metab

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Summary:The effects of the anticholinesterases tetrahy droaminoacridine (THA) and physostigmine on local ce rebral glucose utilization (LCG U) were studied in the conscious rat, using the autoradiographic [14C]deoxyglu cose technique. THA (5 mg/kg i.p.) increased LCGU sig nificantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a metabolic activation in 19 of the 43 regions. LeGU increased in cortical areas (indud ing parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolat era! amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/kg i.p.) reversed the THA induced LeGU increase. Physostigmine (0.2 and 0.5 mg/ kg) increased LeGU in 15 and 22 regions, respectively. The average magnitude of the change induced by 0.5 mg/ Local cerebral glucose utilization (LCGU) is a reliable measure of local cerebral metabolism. De creased LCG U is a consistent finding in dementia of the Alzheimer type (especially in parietal and tem poral cortices) and correlates with the severity of cognitive impairment (Benson et aI., 1983; Fried land et aI., 1985; Duara et aI., 1986).Although deficits in several neurotransmitters oc cur in Alzheimer's disease, the involvement of the cholinergic system seems to be the most severe and the most consistent (Bowen et aI., 1985). Clinical trials attempting to increase the synthesis of acetyl choline (ACh) by the administration of the ACh pre cursors choline or lecithin or to stimulate muscarin- Abbreviations used: ACh, acetylcholine; AChE, acetylcholin esterase; AMB, atropine methylbromide; ChAT, choline acetyl transferase; DG, 2-deoxY-D-glucose; HMB, hexamethonium bromide; LCGU, local cerebral glucose utilization; THA, tet rahydroaminoacridine. 855kg of physostigmine was similar to that observed after THA at 10 mg/kg, but the topography of the effects was somewhat different. Physostigmine increased LeGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal system were smaller than those in duced by THA. The regional topography of the LeGU increase overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity. These data suggest that the major effects of THA and physo stigmine on LCGU result from their anticholinesterase action.

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Learning and memory deficits after lesions of the nucleus basalis magnocellularis: Reversal by physostigmine

Cited by 302 publications

References 21 publications

Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects?

Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects?

Metabolic Response to Tacrine (THA) and Physostigmine in the Aged Rat Brain

Tetrahydroaminoacridine and Physostigmine Increase Cerebral Glucose Utilization in Specific Cortical and Subcortical Regions in the Rat

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