Intravenous nicotine in Alzheimer's disease: a pilot study

Newhouse, Paul; Sunderland, Trey; Tariot, Pierre N.; Blumhardt, C. L.; Weingartner, Herbert; Mellow, Alan M.; Murphy, Dennis L.

doi:10.1007/bf00174504

Cited by 274 publications

(139 citation statements)

References 29 publications

(19 reference statements)

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…In human studies, nicotine has been reported to improve information processing (12,13). Beneficial effects in patients with Alzheimer's disease have even been reported (14). In animal studies, faci litative effects on the delayed matching performance in monkeys has also been reported by other investigators (8).…”

Section: Discussionmentioning

confidence: 88%

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Hironaka

Miyata

Ando

1992

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-To examine the effects of drugs on short-term memory in animals, the delayed discri mination experiment in rats and the delayed matching to sample experiment in rhesus monkeys were conducted. Nicotine at 0.125 mg/kg, s.c. in rats and at 0.5 mg/kg, s.c. in monkeys increased the per centages of correct choices. Scopolamine at 0.06-0.12 mg/kg, s.c. in rats and at 0.015 mg/kg, s.c. in monkeys decreased the percentages of correct choices. However, supposedly memory-specific, delay time-dependent disruptive effects by scopolamine were found only in monkeys. Diazepam at 0.5-2 mg/kg, s.c. did not change the correct choices in rats. However, diazepam at 1-4 mg/kg, i.g. de creased the correct choices in monkeys regardless of the delay time. Chlorpromazine at 0.25-1.5 mg/kg, s.c. showed inconsistent effects in rats. In monkeys, chlorpromazine at 0.25-0.5 mg/kg, s.c. had no effect. These results suggested that using both rats and monkeys would be useful for evaluating the effects of drugs on memory.

show abstract

Section: Discussionmentioning

confidence: 88%

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Hironaka

Miyata

Ando

1992

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…In hu mans, nicotine is reported to increase arousal and at-tention as well as to decrease reaction time, prevent de cline in efficiency over time, and improve the ability to withhold inappropriate responses (Wesnes and War burton, 1983). In pilot studies (Newhouse et al 1988b(Newhouse et al , 1990, we have shown that intravenous nicotine pro duces small but measurable improvements in several cognitive tasks in AD patients. Recently, Jones and col leagues (1992) have shown that acutely administered nicotine can improve attention and speed of informa tion processing in AD patients.…”

mentioning

confidence: 74%

Age-Related Effects of the Nicotinic Antagonist Mecamylamine on Cognition and Behavior

Newhouse

Potter

Corwin³

et al. 1994

Neuropsychopharmacol

131

View full text Add to dashboard Cite

Studies of the neurochemical pathology of Alzheimer's disease and Parkinson's disease reveal a severe and specific loss of central nicotinic cholinergic receptors. We have investigated the functional significance of this finding for cognitive functioning by studying the effects of the centrally active nicotinic antagonist mecamylamine. Single oral doses of mecamylamine were administered to 12 healthy young males and 15 healthy elderly subjects in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. In both groups, the 20-mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition Task, producing a slower acquisition curve. There was no effect of drug on the performance component (retrieval of previously learned information). However, elderly subjects showed en hanced sensitivity to mecamylamine,

show abstract

“…However, neither of these approaches is practicable for projected clinical use, whereas pharmacotherapy with nicotine is. Indeed, nicotine has been used to improve cognitive function in situations of cholinergic deficiency, such as in patients with neurodegenerative diseases (Newhouse et al, 1988), schizophrenia (Rezvani and Levin, 2004), or other situations exhibiting cognitive deficits (White and Levin, 1999). In animal models, nicotine improves hippocampal performance in aged rats with cognitive impairment or in young rats with cholinergic lesions (Levin, 1993).…”

Section: Discussionmentioning

confidence: 99%

Nicotine Therapy in Adulthood Reverses the Synaptic and Behavioral Deficits Elicited by Prenatal Exposure to Phenobarbital

Beer

Slotkin

Seidler

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

A major objective in identifying the mechanisms underlying neurobehavioral teratogenicity is the possibility of designing therapies that reverse or offset drug-or toxicant-induced neural damage. In our previous studies, we identified deficits in hippocampal muscarinic cholinergic receptor-induced membrane translocation of protein kinase C (PKC)g as the likely mechanism responsible for adverse behavioral effects of prenatal phenobarbital exposure. We therefore explored whether behavioral and synaptic defects could be reversed in adulthood by nicotine administration. Pregnant mice were given milled food containing phenobarbital to achieve a daily dose of 0.5-0.6 g/kg from gestational days 9-18. In adulthood, offspring showed deficits in the Morris maze, a behavior dependent on the integrity of septohippocampal cholinergic synaptic function, along with the loss of the PKCg response. Phenobarbital-exposed and control mice then received nicotine (10 mg/kg/day) for 14 days via osmotic minipumps. Nicotine reversed the behavioral deficits and restored the normal response of hippocampal PKCg to cholinergic receptor stimulation. The effects were regionally specific, as PKCg in the cerebellum was unaffected by either phenobarbital or nicotine; furthermore, in the hippocampus, PKC isoforms unrelated to the behavioral deficits showed no changes. Nicotine administration thus offers a potential therapy for reversing neurobehavioral deficits originating in septohippocampal cholinergic defects elicited by prenatal drug or toxicant exposures.

show abstract

Intravenous nicotine in Alzheimer's disease: a pilot study

Cited by 274 publications

References 29 publications

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Age-Related Effects of the Nicotinic Antagonist Mecamylamine on Cognition and Behavior

Nicotine Therapy in Adulthood Reverses the Synaptic and Behavioral Deficits Elicited by Prenatal Exposure to Phenobarbital

Contact Info

Product

Resources

About