BIOL PSYCHIATRY 1989;28:79-82
79
BRIEF R E P O R T
Scopolamine and Olfactory Function Michael Serby, Charles Flicker, Bart Rypma, Scott Weber, John P. Rotrosen, and Steven H. Fen'is
Introduction
Method,';
Several investigators have documented olfac,o tory deficits in Alzheimer's diz~ase (AD) (Serby et al. 1985; Warner et al. 11986, Knupfer and Speigel 1986; Koss et al. 1987; Doty et al. 1987). Preliminary studies have examined the chemical (Serby 1986) and pathological (Averbach 198"~; Esid and Wilcock 1984) correlates of hyposrnia in AD. Acetylcholine (ACh), which has particular relevance to the pathophysiology of AD (Bartus e;~ al. 1982), is an abundant olfactory bulb (OB) neurotransmitter. Furthermore, ACh and bethanechol enhance odor detection when applied to the nasal mucosa in humans (Skouby and ZilstofffPede~en 1954). Thus, it is possible that the olfactory deficits in AD are related to reduced ACh tra~mission. One means of learning more about the neurochemistry of olfaction and of AD is to observe the consequences of pharmacological manipulations. We therefore evaluated the effects of the cholinergic aatagonist scopolamine ~a ~ t h odor detection and odor identification, initially in young normal volunteers.
Thirty volunteers (18-30 years old) signed informed consent and were screened for the presence of standard exclusions for olfactory evaluation (Schiffman !983). Subjects were also excluded for evidence of cardiovascular, affecfive, and cognitive disorders. Subjects wele seen on ~'wo occasions, 1 week apart. In a randomized, double-blind study, each subject received a subcutaneous injection of scopolamine hydrobromide (either 0.22 In = 10], 0.43 In = 10], or 0.65 mg/70 kg In = 10]) on one visit and an equal volume of saline on the other visit. No smoking was permitted for 3 hr prior to the procedure. To evaluate odor identification, the Univerl sity of Pennsylvania Smell Identification Test (UPSIT) (Doty et al. 1984) was administered to all 30 subjects 20 min after injection. This is a standardized 40-odorant task utilizing microencapsulated suprathreshold concentrations of ¢emmon odorants. The subject is instructed to scratch and sniff the strip which contains ~ e odorant and then to identify the correct answer from four supplied possibilities. Odor detection ability was determined by means of a signal detection method requiring the subject to specify the presence or absence of odor produced by geraniol, an dfacto~ stimulant. Twenty-six of the volunteers were :ested 90 min postinjecfion (nine in each of the low- and high-dose scopo!amine groups, ei,ght in the mid-dose group). There were 60 quasi-randomized trials: five trials
From the Department of Psychiatry, New "~ork University School of Medicine (M.S., C.F., S.W., J.P.R., S.H.F.), and Psychiatry Service, New York Veterans Administration Medical Center (M.S., B.R., J.P.R.) New York, NY. Supported by the Veterans Administration. Address reprint requests to Dr. Michael Serby, Department of Psychiatry, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1230 New York, NY 10029-6574. Received October 22, 1988; revised May 6, 1989.
© 1990 Society of Biological Psychiatry
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0006-3,23/90 . . . . . Jv
80
Brief Reports
BIOL PSYCHIATRY 1989;28:79-82
1.50, ns) nor was there a significant drug x dosage group interaction (F[2,23] = 0.13, ns). For the detection measure, scopolamh~e caused a significant impairment compared to piacebo (F[1.231 = 16.18, F < 0.0005). The mean d' was 1.62 - 0.20 (SEM) for the 26 scopolamine trials and 2.60 -+ 0.21 fo~ t~e 26 PBO trials (Figure 1). The effect of scopolamine on detection was not dose dependent, as indicated by the lack of a drug x dosage group interaction (F[2,23] = 0.i7, ns). The impairment in odor detection was noted even at the low dose of scopolamine (F[1,8; = 8.09, p < 0.03) (Figure 2). In contrast, cognitive performance was normal at this dose. (Wicker et al., s~;bmitted for publication). We further assessed ~ differential effects of scopolamine on odor detects:on versus its effects on cognition through a corre~tional analysis, using 6at~.~~n 42 ~ognitive measures derived from the Results assessment battery. In orde,, Lo reduce the egFor the identification task there were ,.;o signif- pe~ment-wis~ ~rror produced by calculating 42 ical~t d:fferences between UPSIT scores (~nean separate correlations, the signi,:4cance level was -+ SEM) lbllowing scca~olamine (37 ~ ± 0.
79
BRIEF R E P O R T
Scopolamine and Olfactory Function Michael Serby, Charles Flicker, Bart Rypma, Scott Weber, John P. Rotrosen, and Steven H. Fen'is
Introduction
Method,';
Several investigators have documented olfac,o tory deficits in Alzheimer's diz~ase (AD) (Serby et al. 1985; Warner et al. 11986, Knupfer and Speigel 1986; Koss et al. 1987; Doty et al. 1987). Preliminary studies have examined the chemical (Serby 1986) and pathological (Averbach 198"~; Esid and Wilcock 1984) correlates of hyposrnia in AD. Acetylcholine (ACh), which has particular relevance to the pathophysiology of AD (Bartus e;~ al. 1982), is an abundant olfactory bulb (OB) neurotransmitter. Furthermore, ACh and bethanechol enhance odor detection when applied to the nasal mucosa in humans (Skouby and ZilstofffPede~en 1954). Thus, it is possible that the olfactory deficits in AD are related to reduced ACh tra~mission. One means of learning more about the neurochemistry of olfaction and of AD is to observe the consequences of pharmacological manipulations. We therefore evaluated the effects of the cholinergic aatagonist scopolamine ~a ~ t h odor detection and odor identification, initially in young normal volunteers.
Thirty volunteers (18-30 years old) signed informed consent and were screened for the presence of standard exclusions for olfactory evaluation (Schiffman !983). Subjects were also excluded for evidence of cardiovascular, affecfive, and cognitive disorders. Subjects wele seen on ~'wo occasions, 1 week apart. In a randomized, double-blind study, each subject received a subcutaneous injection of scopolamine hydrobromide (either 0.22 In = 10], 0.43 In = 10], or 0.65 mg/70 kg In = 10]) on one visit and an equal volume of saline on the other visit. No smoking was permitted for 3 hr prior to the procedure. To evaluate odor identification, the Univerl sity of Pennsylvania Smell Identification Test (UPSIT) (Doty et al. 1984) was administered to all 30 subjects 20 min after injection. This is a standardized 40-odorant task utilizing microencapsulated suprathreshold concentrations of ¢emmon odorants. The subject is instructed to scratch and sniff the strip which contains ~ e odorant and then to identify the correct answer from four supplied possibilities. Odor detection ability was determined by means of a signal detection method requiring the subject to specify the presence or absence of odor produced by geraniol, an dfacto~ stimulant. Twenty-six of the volunteers were :ested 90 min postinjecfion (nine in each of the low- and high-dose scopo!amine groups, ei,ght in the mid-dose group). There were 60 quasi-randomized trials: five trials
From the Department of Psychiatry, New "~ork University School of Medicine (M.S., C.F., S.W., J.P.R., S.H.F.), and Psychiatry Service, New York Veterans Administration Medical Center (M.S., B.R., J.P.R.) New York, NY. Supported by the Veterans Administration. Address reprint requests to Dr. Michael Serby, Department of Psychiatry, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1230 New York, NY 10029-6574. Received October 22, 1988; revised May 6, 1989.
© 1990 Society of Biological Psychiatry
~t
.~N'2
cn
0006-3,23/90 . . . . . Jv
80
Brief Reports
BIOL PSYCHIATRY 1989;28:79-82
1.50, ns) nor was there a significant drug x dosage group interaction (F[2,23] = 0.13, ns). For the detection measure, scopolamh~e caused a significant impairment compared to piacebo (F[1.231 = 16.18, F < 0.0005). The mean d' was 1.62 - 0.20 (SEM) for the 26 scopolamine trials and 2.60 -+ 0.21 fo~ t~e 26 PBO trials (Figure 1). The effect of scopolamine on detection was not dose dependent, as indicated by the lack of a drug x dosage group interaction (F[2,23] = 0.i7, ns). The impairment in odor detection was noted even at the low dose of scopolamine (F[1,8; = 8.09, p < 0.03) (Figure 2). In contrast, cognitive performance was normal at this dose. (Wicker et al., s~;bmitted for publication). We further assessed ~ differential effects of scopolamine on odor detects:on versus its effects on cognition through a corre~tional analysis, using 6at~.~~n 42 ~ognitive measures derived from the Results assessment battery. In orde,, Lo reduce the egFor the identification task there were ,.;o signif- pe~ment-wis~ ~rror produced by calculating 42 ical~t d:fferences between UPSIT scores (~nean separate correlations, the signi,:4cance level was -+ SEM) lbllowing scca~olamine (37 ~ ± 0.
