Abstract
In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.5 μg/kg/min) of intravenous nicotine and placebo. Cognitive tests showed a decrease in intrusion errors on the middle (0.25 μg) dose. Prominent behavioral effects were noted, with significant dose-related increases in anxiety and depressive affect. These results suggest that central nicotinic cholinergic stimulation deserves further investigation as a treatment in Alzheimer's disease and that nicotine may also be a useful investigative tool in other populations as a probe of central cholinergic function, especially in regard to the modulation of affect.
This is a preview of subscription content, access via your institution.
References
Battig W, Montague N (1969) Category norms for verbal items in 56 categories. J Exp Psychol [Monogr] 80:1–43
Coyle JT, Price DL, DeLong MR (1983) Alzheimer's disease: a disorder of cholinergic innervation. Science 219:1184–1190
Davis KL, Hollander E, Davidson M, Davis BM, Mohs RC, Horvath TB (1987) Induction of depression with oxotremorine in patients with Alzheimer's disease. Am J Psychiatry 144:468–471
Flynn DD, Mash DC (1986) Characterization of 1-[3H] nicotine binding in cerebral cortex: comparison between Alzheimer's disease and the normal. J Neurochem 47:1948–1954
Fuld PA, Katzman R, Davies P, Terry RD (1982) Intrusions as a sign of Alzheimer dementia: chemical and pathological verification. Ann Neurol 11:155–159
Gonzalez LP, Altschuler HL (1979) Scopolamine effects on suppression of operant responding. Physiol Psychol 7:156–162
Gottfries CG (1985) Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. Psychopharmacology 86:245–252
Janowsky DS, Risch SC (1984) Cholinomimetic and anticholinergic drugs used to investigate an acetylcholine hypothesis of affective disorders and stress. Drug Dev Res 4:125–142
Ksir C, Benson DM (1983) Enhanced behavioral response to nicotine in an animal model of Alzheimer's disease. Psychopharmacology 81:272–273
McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T (1984) Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 34:741–745
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group. Neurology 34:939–944
Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarinic receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 228:1115–1117
Mohs RC, Davis BM, Greenwald BS, Mathe AA, Johns CA, Horvath TB, Davis KL (1985) Clinical studies of the cholinergic deficit in Alzheimer's disease II: psychopharmacologic studies. J Am Geriatr Soc 33:749–757
Murphy DL, Pickar D, Alterman IS (1982) Methods for quantitative assessment of depressive and manic behavior. In: Burdock EI, Sudilovsky A, Gershon S (eds) The behavior of psychiatric patients. Dekker, New York, pp 355–391
Newhouse PA, Sunderland T, Thompson K, Tariot PN, Weingartner H, Murphy DL (1986a) Dose related physiologic, behavioral, and cognitive effects of nicotine on naive human subjects. Neurosci Abstr 12(2):1445
Newhouse PA, Sunderland T, Thompson K, Tariot PN, Weingartner H, Mueller ER, Cohen RM, Murphy DL (1986b) Intravenous nicotine in a patient with Alzheimer's disease. Am J Psychiatry 143:1494–1495
Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10:799–812
Perry EK, Perry RH, Smith CJ, Dick DJ, Candy JM, Edwardson JA, Fairbairn A, Blessed G (1987) Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases. J Neurol Neurosurg Psychiatry 50:806–809
Reisberg B, Ferris SH, DeLean MJ, Crook T (1982) The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 139:1136–1139
Schwartz RD, Kellar KJ (1982) Nicotinic cholinergic receptors labeled by [3H]-acetylcholine in rat brain. Mol Pharmacol 22:55–62
Shimohama S, Taniguchi T, Fujiwara M, Kameyama M (1985) Biochemical characterization of the nicotinic cholinergic receptors in human brain: binding of (—)-[3H] nicotine. J Neurochem 45:604–610
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med 315:1241–1245
Sunderland T, Tariot PN, Weingartner H, Murphy DL, Newhouse PA, Mueller EA, Cohen RM (1986) Pharmacologic modelling of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 10:599–610
Tariot PN, Cohen RM, Welkowitz JA, Sunderland T, Newhouse PA, Murphy DL, Weingartner H (1988) Multiple dose arecoline infusions in Alzheimer's disease. Arch Gen Psychiatry (in press)
Van Kammen DP, Murphy DL (1975) Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Psychopharmacology 44:215–224
Vitaliano PP (1982) Parametric statistical analysis of repeated measures experiments. Psychoneuroendocrinology 7:3–13
Warburton DM, Wesnes K (1985) Historical overview of research on cholinergic systems and behavior. In: Singh MM, Warburton DM, Lal H (eds) Central cholinergic mechanisms and adaptive dysfunctions. Plenum Press, New York, pp 1–36
Warburton DM, Wesnes K, Shergold K, James M (1986) Facilitation of learning and state dependency with nicotine. Psychopharmacology 89:55–59
Wesnes K, Revell A (1984) The separate and combined effects of scopolamine and nicotine on human information processing. Psychopharmacology 84:5–11
Wesnes K, Warburton DM (1983) Smoking, nicotine, and human performance. Pharmacol Ther 21:189–208
Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing. Psychopharmacology 82:147–150
Whitehouse PJ, Martino AM, Antuono PG, Lowenstein PR, Coyle JT, Price DL, Kellar KJ (1986) Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Res 371:146–151
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Newhouse, P.A., Sunderland, T., Tariot, P.N. et al. Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology 95, 171–175 (1988). https://doi.org/10.1007/BF00174504
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00174504
Key words
- Alzheimer's disease
- Nicotine
- Central cholinergic stimulation