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Attenuation of scopolamine-induced cognitive impairments by dextroamphetamine in young normals
Basic and Clinical Psychopharmacology
BIOL PSYCHIATRY 1990;27:4!A- 179A
89A
° " ...... °""" needs to be considered. There are. however, detectable quantities of D2 ,"eceptors neuroleptic re,Am in human cortex.
108 NOREPINEPHRINE AND CORTISOL RESPONSES TO NATURALISTIC STRESSORS IN ACUTE AND REMITTED DEPRESSION Robert L. Trestman, Ph.D., M.D., Emil Coccaro, M.D., David Bemstein, M.A., Timothy Lawrence, M.D., Thomas Horvath, M.D., Larry J. Siever, M.D. Veterans Affairs Medical Center, Bronx, NY, and Department of Psychiatry, Mount Sinai School of Medicine, New York. NY 10029. The pattern ofcortisoi or norepinephrine (NE) response to naturalistic stressors was evaluated in 22 depressed (MDD) male patients (13 acutely depressed [MDD-A] and 9 remitted depressed [MDD-R] and in 12 ageand gender-matched controls. The response of NE to isometric exertion after orthos~atie challenge was significantly reduced in MDD patients (p < 0.05) and in acute but not remitted patients compared with controls (p < 0.05). Basal plasma cortisol levels were found to be state dependent (MDD-A > MDD-R, p < 0.03), whereas the peak plasma cortisol response at 30 min to a mental arithmetic task (MAT), adjusted for initial differences in plasma cortisol, was state independent: cortisol response in MDD was lower than controls (p < 0.05), but no significant differences were observe~ between MDD-A and MDD-R. To determine the contribution of underlying diurnal cortisol levels, samples were drawn at matched times on a separate, nonstress day. When this diurnal variation was subtracted from the cortisol response to MAT, the relations were unchanged. Similar results were found in a repeated-measurement analysis over the 1.5 hour protocol. These findings suggest that enduring noradrenergic/neuroendocriae disturbances in depression may be unmasked by naturalistic challenges and may be state independent in certain contexts.
109 ATTENUATION OF SC'3POLAMINE-INDUCED COGNITIVE IMPAIRMENTS BY DEXTROAMPHETAMINE IN YOUNG NORMALS R.A. Martinez, M.D., S.E. Molchan, M.D., G.S. Latham, M.D., B.A. Lawlor, M D., J.L. Hill, Ph.D., H.J. Weingartner, Ph.D., and T. Sunderland, M.D. Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. We have previously demonstrated that scopolamine (SCOP) can produce a significant temporary memory impairment that mimics Alzheimer's disease (Sunderland et al., 1986) and that the neumpeptide, T R H , partially attenuates this impairment (Molchan et al. [in press]). In this current study, we tested d-amphetamine (D-AMP) to examine how its stimulant properties alter the memory effects of SCOP. Eleven healthy volunteers (mean age 28.5 __. 1.5 years) received SCOP (0.5 mg intravenously) with or without D-AMP (0.25 mg/kg body weight) in a randomized, double-blind paradigm. Statistically significant improvement was observed on days in which subjects received SCOP + D-AMP (versus SCOP alone) in measures of knowledge memory (i.e., verbal fluency for categories and letters) (p < 0.04) and recognition memory (i.e., ability to recognize distractor stimuli) (p < 0.04). A modest but statistically nonsignificant improvement on immediate recall (i.e., Buschke task) was also noted in this preliminary group of subjects. Objective measures of fatigue were significantly diminished on days in which subjects received SCOP + D-AMP (versus SCOP alone) (p < 0.05); however, reaction time measurements did not differ among drug days. These results indicate that D-AMP partially reverses SCOP-induced impairments of knowledge and recognition memory, an effect that may ~ partially explained by its activating effects, although direct catecholaminergic influences on the cholinergic system cannot be ruled out. Further studies using larger doses of D-AMP are necessary to determine whether this drug will be of any potential therapeutic benefit in neurodegenerative disorders such as Alzheimer~s disease.
BIOL PSYCHIATRY 1990;27:4!A- 179A
89A
° " ...... °""" needs to be considered. There are. however, detectable quantities of D2 ,"eceptors neuroleptic re,Am in human cortex.
108 NOREPINEPHRINE AND CORTISOL RESPONSES TO NATURALISTIC STRESSORS IN ACUTE AND REMITTED DEPRESSION Robert L. Trestman, Ph.D., M.D., Emil Coccaro, M.D., David Bemstein, M.A., Timothy Lawrence, M.D., Thomas Horvath, M.D., Larry J. Siever, M.D. Veterans Affairs Medical Center, Bronx, NY, and Department of Psychiatry, Mount Sinai School of Medicine, New York. NY 10029. The pattern ofcortisoi or norepinephrine (NE) response to naturalistic stressors was evaluated in 22 depressed (MDD) male patients (13 acutely depressed [MDD-A] and 9 remitted depressed [MDD-R] and in 12 ageand gender-matched controls. The response of NE to isometric exertion after orthos~atie challenge was significantly reduced in MDD patients (p < 0.05) and in acute but not remitted patients compared with controls (p < 0.05). Basal plasma cortisol levels were found to be state dependent (MDD-A > MDD-R, p < 0.03), whereas the peak plasma cortisol response at 30 min to a mental arithmetic task (MAT), adjusted for initial differences in plasma cortisol, was state independent: cortisol response in MDD was lower than controls (p < 0.05), but no significant differences were observe~ between MDD-A and MDD-R. To determine the contribution of underlying diurnal cortisol levels, samples were drawn at matched times on a separate, nonstress day. When this diurnal variation was subtracted from the cortisol response to MAT, the relations were unchanged. Similar results were found in a repeated-measurement analysis over the 1.5 hour protocol. These findings suggest that enduring noradrenergic/neuroendocriae disturbances in depression may be unmasked by naturalistic challenges and may be state independent in certain contexts.
109 ATTENUATION OF SC'3POLAMINE-INDUCED COGNITIVE IMPAIRMENTS BY DEXTROAMPHETAMINE IN YOUNG NORMALS R.A. Martinez, M.D., S.E. Molchan, M.D., G.S. Latham, M.D., B.A. Lawlor, M D., J.L. Hill, Ph.D., H.J. Weingartner, Ph.D., and T. Sunderland, M.D. Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. We have previously demonstrated that scopolamine (SCOP) can produce a significant temporary memory impairment that mimics Alzheimer's disease (Sunderland et al., 1986) and that the neumpeptide, T R H , partially attenuates this impairment (Molchan et al. [in press]). In this current study, we tested d-amphetamine (D-AMP) to examine how its stimulant properties alter the memory effects of SCOP. Eleven healthy volunteers (mean age 28.5 __. 1.5 years) received SCOP (0.5 mg intravenously) with or without D-AMP (0.25 mg/kg body weight) in a randomized, double-blind paradigm. Statistically significant improvement was observed on days in which subjects received SCOP + D-AMP (versus SCOP alone) in measures of knowledge memory (i.e., verbal fluency for categories and letters) (p < 0.04) and recognition memory (i.e., ability to recognize distractor stimuli) (p < 0.04). A modest but statistically nonsignificant improvement on immediate recall (i.e., Buschke task) was also noted in this preliminary group of subjects. Objective measures of fatigue were significantly diminished on days in which subjects received SCOP + D-AMP (versus SCOP alone) (p < 0.05); however, reaction time measurements did not differ among drug days. These results indicate that D-AMP partially reverses SCOP-induced impairments of knowledge and recognition memory, an effect that may ~ partially explained by its activating effects, although direct catecholaminergic influences on the cholinergic system cannot be ruled out. Further studies using larger doses of D-AMP are necessary to determine whether this drug will be of any potential therapeutic benefit in neurodegenerative disorders such as Alzheimer~s disease.