Effects of cholinergic drugs on learning impairment in ventral globus pallidus-lesioned rats

Ueki, Akinori; Miyoshi, Koho

doi:10.1016/0022-510x(89)90041-5

Cited by 52 publications

(22 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Electrolytic or neurotoxic lesions of the nucleus basalis magnocellularis (NBM) reduce cortical ChAT activity, AChE activity, acetylcholine (ACh) release and choline uptake (21)(22)(23). Moreover, NBM-lesioned rats showed impaired acquisition of a passive avoidance response (24). These data should be useful for establishing a model of Alzheimer's disease which could be used to study thera peutic drugs and methods.…”

mentioning

confidence: 99%

Age-Related Changes of Cholinergic Markers in the Rat Brain

Yufu

Egashira

Yamanaka

1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-de pendent high affinity choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H]-QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed.[3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vma, values of ChAT and AChE also decreased about 20-30076 compared with those of young rats. The sodium-dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 pM 10 nM, but choline uptake in aged brain was insensitive to hemicholinium-3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons.

show abstract

mentioning

confidence: 99%

Age-Related Changes of Cholinergic Markers in the Rat Brain

Yufu

Egashira

Yamanaka

1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…NIK-247 and THA are reported to be effec tive on drug-induced amnesia at 0.03-1 mg/kg in animal experiments (4,5). In rats, THA at 10 mg/kg, p.o.…”

Section: Discussionmentioning

confidence: 99%

“…Because involvement of the neuronal cholinergic system has been suggested in learning and memory (2), possi ble therapeutic use of NIK-247 in this respect has been explored. Studies have indicated that NIK-247 facilitates memory acquisition and re trieval in mice (3) and improves drug-induced amnesia in mice and rats (4,5). It has been well-established that THA (9-amino-1,2,3,4 tetrahydro-acridine hydrochloride hydrate), a related AChE inhibitor, improves cognitive function and memory (6,7) and facilitates synaptic transmission in the cholinergic system (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

NIK-247 Blocks Voltage-Dependent Ionic Currents in Crayfish Axon.

1991

View full text Add to dashboard Cite

3,5,6,7,-quinoline hydrochloride hydrate), an acetylcholinesterase inhibitor, is structurally related to 4 aminopyridine (AP). Its effects on ionic currents were examined in the artificial node of the crayfish axon under voltage-clamp. When applied externally, NIK-247 revers ibly suppressed both inward and outward currents. Effects on K currents were further studied in the presence of tetrodotoxin. NIK-247 suppressed the K current dose-de pendently, but with an IC50 at of 10-3 M. THA (9-amino-1,2,3,4-tetra-hydroacridine hydrochloride hydrate), a related inhibitor, similarly suppressed the K current with an IC50 of 5 X 10-4 M, in comparison with 3-AP and 4-AP which had IC50's of 3 X 10-5 M and at 10-5 M, respectively. Furthermore, NIK-247 (and THA) suppressed the K current uniformly for the whole time course, whereas AP the AP's suppressed mainly the fast activating and inactivating K current with a voltage and frequency-dependent recovery. Therefore, NIK-247 and THA seem to be neither potent nor very specific as ionic channel blockers. With respect to the K current, however, they clearly differ from the AP's in their mode of suppression.

show abstract

“…NIK-247 (9-amino 2,3,5,6,7,8-hexahydro-1H-cyclopenta [b]quinoline mono hydrochloride monohydrate) has been reported to inhibit acetylcholinesterase (AChE) (5) and to improve learning and memory performance in animal studies (6)(7)(8)(9)(10). Oral administration of NIK-247 increases ACh content in the brain and increases ACh efflux from brain slices (5,11).…”

mentioning

confidence: 99%

Effect of NIK-247 on Basal Concentrations of Extracellular Acetylcholine in the Cerebral Cortex of Conscious, Freely Moving Rats

Ishii

Kojima

Ikeda

et al. 1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-We studied the effect of orally administered 3,5,6,7,quinoline monohydrochloride monohydrate) on basal extracellular acetylcholine (ACh) con centrations in the rat cerebral cortex using microdialysis without the addition of cholinesterase inhibitor to the perfusion fluid and radioimmunoassay for ACh. In addition, the effect of oral administration of NIK 247 on acetylcholinesterase (AChE) activity in rat cerebral cortex was determined. The mean basal ACh con tent in the perfusate from the cerebral cortex of freely moving rats was 123.2±21.8 fmol/30 min (n=7). NIK-247 (2.5 10.0 mg/kg, p.o.) increased the ACh content of the perfusate in a dose-dependent manner. NIK-247 at 10 mg/kg significantly increased the ACh content in the perfusate from 0.5 to 2.5 hr after administration, and the maximum increase was attained at 1 hr after administration. 9-Amino-1,2,3,4 tetrahydroacridine (5 mg/kg, p.o.) and physostigmine (0.5 mg/kg, i.p.) significantly increased the ACh con tent in the perfusate from 1 to 2 hr and from 0.5 to 1.5 hr after administration, respectively. AChE activities in the cerebral cortex were about 32070 and 1207o below the control value at 1 hr and 3 hr after administration of NIK-247 at 10 mg/kg, respectively. These findings demonstrate that NIK-247 increases extracellular ACh concentration and inhibits AChE activity in the cerebral cortex after oral administration, and they suggest that NIK-247 facilitates central cholinergic transmission.

show abstract

Effects of cholinergic drugs on learning impairment in ventral globus pallidus-lesioned rats

Cited by 52 publications

References 14 publications

Age-Related Changes of Cholinergic Markers in the Rat Brain

Age-Related Changes of Cholinergic Markers in the Rat Brain

NIK-247 Blocks Voltage-Dependent Ionic Currents in Crayfish Axon.

Effect of NIK-247 on Basal Concentrations of Extracellular Acetylcholine in the Cerebral Cortex of Conscious, Freely Moving Rats

Contact Info

Product

Resources

About