Biomedical subjects

M A Raskind

Publications and source records attributed to M A Raskind.

At least 55 records · Page 3Linked to original sources

PubMed1997

Nerve growth factor induces galanin gene expression in the rat basal forebrain: implications for the treatment of cholinergic dysfunction.

Nerve growth factor (NGF) is a potential treatment for cholinergic dysfunction associated with Alzheimer's disease (AD). In rats, NGF activates gene expression of the acetylcholine synthetic enzyme choline acetyltransferase (ChAT) and prevents age- and lesion-induced degeneration of basal forebrain (BF) cholinergic neurons. Cholinergic neurons in the BF coexpress galanin (GAL), a neuropeptide that has been shown to impair performance on memory tasks possibly through the inhibition of cholinergic memory pathways. NGF up-regulates both ChAT and GAL gene expression in cultured pheochromocytoma cells; however, the effect of chronic in vivo NGF administration on GAL gene expression within the BF has not been studied. We used in situ hybridization and quantitative autoradiography to assess GAL and ChAT gene expression within the BF of adult male rats following chronic intracerebroventricular infusion of NGF or cytochrome c. We now report that, in addition to stimulating ChAT gene expression, NGF strongly up-regulated the GAL gene in the rat cholinergic BF. NGF had no effect on GAL gene expression in other noncholinergic forebrain regions. NGF induction of GAL gene expression in the BF was specific, because gene expression for another neuropeptide, neurotensin, present within noncholinergic BF neurons was unchanged. Our data provide the first evidence that in vivo NGF administration up-regulates GAL gene expression in the cholinergic BF. These results suggest that the concurrent induction of GAL in the BF could limit the ameliorating actions of NGF on cholinergic dysfunction.

Animals↗

PubMed1997

The effect of apolipoprotein E genotype on expression of an autosomal dominant schizophreniform disorder with progressive dementia and neurofibrillary tangles.

The apolipoprotein E (APOE) epsilon 4 allele is associated with an increased and the epsilon 2 allele a decreased risk for Alzheimer's disease (AD). It has been hypothesized that these risks are mediated by differential effects of the APOE alleles on the cytoskeletal degeneration, which results in neurofibrillary tangle (NFT) formation. It has also been suggested that APOE alleles differentially affect the beta amyloid accumulation. We examined APOE genotypes and their effects on age of onset in a family with an autosomal dominant "neurofibrillary tangle only" dementia. This disorder is manifested by schizophreniform psychosis followed by progressive dementia and neuropathologically by prominent AD-like neurofibrillary tangles without neuritic plaques. The only affected epsilon 4 heterozygote in this family did not demonstrate accelerated disease onset. In contrast, the affected epsilon 2 heterozygote had the latest age of onset of any affected family member. The two other epsilon 2 heterozygotes remained unaffected at an age much greater than the mean age of onset for the disease. These results are consistent with a protective effect of the epsilon 2 allele in a hereditary neuropsychiatric disorder with prominent NFT formation.

Alleles↗

PubMed1997

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease.

OBJECTIVE: To examine the effects of tacrine hydrochloride in patients with Alzheimer disease (AD) and detectable baseline deficits in discrete cognitive and noncognitive parameters who are enrolled in a previously reported multicenter, double-blind, 30-week trial. DESIGN: An exploratory analysis using last observation carried forward. The study population included a placebo group (n = 181) and all patients randomized to treatment within 160 mg/d of tacrine hydrochloride (n = 234), regardless of highest dose achieved or duration of tacrine therapy. STUDY POPULATION: Male and female subjects, at least 50 years of age, with mild to moderate AD and detectable baseline deficits in discrete cognitive and noncognitive parameters. MAIN OUTCOME MEASURES: Change from baseline to last observation carried forward in discrete subscale scores of the Alzheimer's Disease Assessment Scale (ADAS): cognitive (memory, language, praxis) and noncognitive (mood, behavior). Improvement was defined as a decrease of at least 1 point from baseline; stabilization was defined as no change or a decrease from baseline. RESULTS: Compared with the placebo group, the percentage of patients receiving tacrine whose conditions improved or stabilized was significantly greater for 8 of 11 ADAS-cognitive items (word recall, word recognition, orientation, language production, comprehension, word finding, following commands, ideational praxis) and for the ADAS-noncognitive items: cooperation, delusions, and pacing. CONCLUSIONS: Tacrine stabilizes or improves specific behavioral deficits and symptoms in AD. The previous demonstration of tacrine's effect on global cognitive function has been extended by suggesting an association between tacrine therapy and improvements in individual cognitive and noncognitive items of the ADAS. Effects of tacrine in clinical practice might be more accurately and efficiently assessed by measuring individual ADAS cognitive and noncognitive items relevant to individual patient pretreatment clinical status.

Aged↗

PubMed1997

The Caregiver Activity Survey (CAS): development and validation of a new measure for caregivers of persons with Alzheimer's disease.

BACKGROUND: Most instruments that measure the impairments associated with Alzheimer's disease assess symptom severity. Little attention has been paid to the illness's impact on the time formal and informal caregivers spend caring for Alzheimer's individuals. A tool that measures the time spent caregiving would help to determine the economic impact of the illness. The Caregiver Activity Survey (CAS) was developed to measure the time caregivers spend aiding Alzheimer's patients with their day-to-day activities. METHODS: The test-retest reliability of the CAS was assessed during a 3-week study with 42 Alzheimer's patients and their caregivers. The CAS was validated with the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog), the Mini Mental State Exam (MMSE) and the Physical Self Maintenance Scale (PSMS). RESULTS: The final version of the CAS consists of six items (communicating with the person, using transportation, eating, dressing, looking after one's appearance and supervising the person). The six-item CAS total score has high test-retest reliability, with ICC = 0.88 between weeks 1 and 3. The scale has strong convergent validity with the ADAS-Cog (r = 0.61), MMSE (r = -0.57) and PSMS (r = 0.43). Efforts to include a dimension that reflects caregiver burden were not successful, in part due to the reluctance of caregivers to acknowledge that caregiving is bothersome. CONCLUSIONS: The CAS provides a new tool that measures time spent caring for Alzheimer's individuals. The instrument may be used to augment existing clinical assessments that measure the efficacy of potentially therapeutic agents for persons with Alzheimer's disease.

Activities of Daily Living↗

PubMed1997

Cerebrospinal fluid and plasma disposition of yohimbine and 11-hydroxy-yohimbine in young and older healthy subjects, and Alzheimer's disease patients.

OBJECTIVE: The plasma and cerebrospinal fluid (CSF) disposition of yohimbine (YO) and 11-hydroxy-yohimbine (11-OH-YO), after oral administration of a single dose of YO (0.65 mg.kg-1) were studied in young and older healthy subjects and in patients with Alzheimer's disease (AD). RESULTS: Plasma disposition of YO displayed large variability; no significant differences among subject groups were observed. In contrast, 11-OH-YO Cmax and AUC were significantly lower in the older normal subjects than in the young normal or AD subjects. A strong positive correlation between CSF and plasma YO concentrations was observed. A weak positive correlation between CSF and plasma concentrations of 11-OH-YO was also observed. CSF to plasma concentration ratios for yohimbine and 11-OH-YO were low (approximately 2%).

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1997

Decreased hypothalamic-pituitary-adrenal axis sensitivity to cortisol feedback inhibition in human aging.

Aging-related reduction in the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to glucocorticoid feedback inhibition has been demonstrated in rodents, but aging effects on glucocorticoid feedback inhibition in humans are unclear. This study assessed the influence of aging on the sensitivity of the human HPA axis to feedback inhibition induced by cortisol. Endogenous cortisol feedback inhibition was removed by treatment with metyrapone, which reduces cortisol synthesis by inhibiting 11 beta-hydroxylase. Feedback inhibition was then reintroduced by infusing exogenous cortisol. Sixteen young (26 +/- 1 years old) and 16 older (70 +/- 2 years old) subjects underwent three study conditions in random order. In the two cortisol infusion conditions, oral metyrapone treatment was followed by intravenous infusion of 0.03 mg/kg/h (83 nmol/kg/h) or 0.06 mg/kg/h (166 nmol/kg/h) cortisol for 150 min. Feedback sensitivity was estimated by the latency to and extent of decline of plasma ACTH concentration during and following the cortisol infusion. In a placebo condition, placebo tablets were substituted for metyrapone and normal saline infusion was substituted for cortisol. Blood samples were drawn twice prior to and at 15-min intervals for 4 h following the onset of the infusions, and plasma was assayed for 11-deoxycortisol, cortisol and ACTH. Plasma cortisol suppression and ACTH and 11-deoxycortisol elevations did not differ between age groups after metyrapone. Older subjects exhibited delayed and blunted ACTH responses to infused cortisol. Within older subjects, the ACTH response to the higher dose cortisol infusion was blunted in older women compared to older men. These data provide direct evidence for reduced responsiveness to glucocorticoid feedback inhibition in human aging.

Adrenal Glands↗

PubMed1997

Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration.

OBJECTIVE: Although loss of noradrenergic neurons in the locus ceruleus has been consistently demonstrated postmortem in Alzheimer's disease, several small studies suggest that indices of central noradrenergic activity increase with the severity of Alzheimer's disease in living patients. The authors estimated the effect of Alzheimer's disease severity on central noradrenergic activity by comparing the CSF norepinephrine concentrations of subjects with Alzheimer's disease in earlier and advanced stages. The effect of normal aging on CSF norepinephrine also was determined. METHOD: Lumbar punctures were performed in 49 subjects with Alzheimer's disease of mild or moderate severity, 25 subjects with advanced Alzheimer's disease, 42 normal older subjects, and 54 normal young subjects. Advanced Alzheimer's disease was defined prospectively by a Mini-Mental State score of less than 12. Norepinephrine was measured by radioenzymatic assay. RESULTS: CSF norepinephrine concentration was significantly higher in the patients with advanced Alzheimer's disease (mean = 279 pg/ml, SD = 122) than in those with mild to moderate severity (mean = 198 pg/ml, SD = 89), normal older subjects (mean = 219 pg/ml, SD = 88), or normal young subjects (mean = 154 pg/ml, SD = 53). CSF and plasma norepinephrine levels and mean arterial blood pressure all were higher in the older subjects than in the young subjects. CONCLUSIONS: Despite the loss of locus ceruleus neurons in Alzheimer's disease, the aging-associated high concentration of CSF norepinephrine is retained in the earlier stages of Alzheimer's disease and increases further as the disease progresses. Increased brain noradrenergic activity may contribute to the agitated behaviors or cognitive deficits of patients with advanced Alzheimer's disease.

Adult↗

PubMed1997

Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder.

OBJECTIVE: Sodium lactate infusion has induced flashbacks accompanied by panic attacks in male combat veterans with posttraumatic stress disorder (PTSD) and concurrent panic disorder. This study addressed whether sodium lactate induces flashbacks or other intrusive PTSD symptoms in PTSD patients free of concurrent panic disorder. METHOD: Behavioral, cardiovascular, catecholamine, and cortisol responses to infusion of 0.5 M sodium lactate were compared among seven subjects with PTSD without panic disorder, seven subjects with panic disorder only, and seven healthy subjects. RESULTS: Six of the seven PTSD subjects but no panic disorder or healthy subjects reported flashbacks or other intrusive PTSD symptoms during lactate infusion. Flashbacks were accompanied by substantial anxiety symptoms. Cortisol levels were low in the PTSD subjects. CONCLUSIONS: Sodium lactate induces flashbacks in persons with PTSD without comorbid panic disorder. The relationship between anxiety responses accompanying a PTSD flashback and those in a panic attack remains unclear.

Adult↗

PubMed1997

Clinical features and pharmacologic treatment of behavioral symptoms of Alzheimer's disease.

Behavioral symptoms are an integral component of Alzheimer's disease (AD) and an important cause of failure of home care. Well-chosen pharmacologic and psychosocial treatments can improve many of the distressing problem behaviors that occur in the course of the disease and, in some cases, may delay institutionalization. However, controlled trials remain scarce, and prediction of treatment outcome for individual patients is still uncertain at best. Recent improvements in the characterization of behavioral syndromes in AD hold promise for increasing the specificity of treatment choice and the predictability of response. This article reviews features of the major behavioral problems associated with AD and evidence for the effectiveness of existing treatments. We argue that the origins of behavioral disturbances include both intrinsic neurobiological aspects of the disease and environmental provocations, and present an approach to treatment decision-making that respects both the clinician's need to intervene to reduce suffering and the limitations of current knowledge.

Alzheimer Disease↗

PubMed1997

Clinicopathologic correlations of soluble amyloid beta-protein precursor in cerebrospinal fluid in patients with Alzheimer disease and controls.

The authors compared concentrations of soluble beta-amyloid protein precursor (s beta PP) in cerebrospinal fluid (CSF) in 45 patients diagnosed with probable Alzheimer disease (AD) and 26 normal older control volunteers. Soluble beta-amyloid protein precursor concentrations were measured in 125 CSF samples using an enzyme-linked immunosorbent assay. All subjects had Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDRS) scores and assessment of disease duration. The s beta PP concentrations in CSF in the probable AD group (mean +/- SD = 493 +/- 268 micrograms/L) were decreased significantly compared with the age-matched control group (mean = 831 +/- 302 micrograms/L; p < 0.0001). In the probable AD group, MMSE scores correlated positively with s beta PP concentrations (correlation coefficient r = 0.53, p < 0.0001), and CDRS ratings and disease duration correlated inversely with s beta PP concentrations (r = -0.59, p < 0.0001 and r = -0.479, p = 0.0006, respectively). Although the decrease in CSF s beta PP from levels found in healthy elderly controls was significant in AD subjects, there was substantial overlap. In AD, CSF s beta PP was most reduced in patients in later stages of the disease. The s beta PP concentrations reflect disease severity, but utility in differential diagnosis has not been determined.

Aged↗

PubMed1996

Galanin gene expression declines with adulthood in the cholinergic fields of the horizontal diagonal band of male rats.

The neuropeptide galanin (GAL) influences learning and memory processes, perhaps by inhibiting cholinergic function. We recently reported that, in the rat, the nucleus of the horizontal limb of the diagonal band (HDB) exhibits the highest level of GAL mRNA coexpression by basal forebrain (BF) cholinergic neurons and, in the HDB, virtually all GAL mRNA-expressing neurons correspond to the cholinergic cell type. Since GAL gene expression is induced across puberty in many brain regions, we used in situ hybridization histochemistry and quantitative autoradiography to assess GAL gene expression across the rostro-caudal extent of the HDB in prepubertal and adult male rats and to determine whether GAL gene expression is also regulated during maturation in this BF region. Our results show that the number of GAL mRNA-expressing cells per section is significantly reduced in the HDB with adulthood. Post-hoc analysis indicated that these age-associated differences in the number of GAL mRNA-expressing cells per section could be ascribed to the rostral and central subregions of the HDB. Age-related differences in the labeling intensity of GAL mRNA-expressing neurons were also detected in the rostral and central subregions of the HDB. No age-associated differences in GAL gene expression were found in the caudal HDB subregion. These results suggest that: (1) in contrast to other brain regions, GAL gene expression in the cholinergic BF may be negatively regulated by factors concomitant with puberty; and (2) the inhibition of cholinergic function by cosecreted GAL may be enhanced prior to puberty within cholinergic neurons of the rostral and central aspects of the HDB.

Acetylcholine↗

PubMed1996

Hypothalamic-pituitary-adrenocortical axis responses to physostigmine: effects of Alzheimer's disease and gender.

We asked whether hypothalamic-pituitary-adrenocortical (HPA) axis responses to a cholinergic stimulus are blunted in patients with Alzheimer's disease (AD) of mild to moderate severity. Such a finding would be consistent with a central cholinergic deficiency early in the course of AD. To address this question, we measured the plasma adrenocorticotropic hormone (ACTH), beta-endorphin-like immunoreactivity (beta E-LI), and cortisol responses to the cholinesterase inhibitor physostigmine in 10 healthy normal older subjects (age = 71 +/- 2 years) and 11 outpatients with probable AD (age = 72 +/- 2 years; Mini Mental State Exam score = 19 +/- 2). Cortisol concentrations were higher in AD subjects throughout the study, but AD and normal older subjects had similar robust ACTH, beta E-LI, and cortisol responses to physostigmine. In all subjects combined, women had greater ACTH, beta E-LI, and cortisol responses to physostigmine than did men. Plasma physostigmine concentrations did not differ between groups. These results suggest that female gender enhances the magnitude of HPA axis responses to cholinergic stimulation in older humans; however, the HPA axis response to physostigmine does not appear to reflect central cholinergic deficiency in the early stages of AD.

Adrenal Cortex Hormones↗

PubMed1996

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease.

A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. The Alzheimer's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures. Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints. In addition, early-onset patients tended to decline more rapidly than older patients in the placebo groups. Conversely, late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients. The drug was very well tolerated during the trial. The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly. However, these preliminary findings are based on past hoc analyses. A prospective trial of ALCAR in younger patients is underway to test the hypothesis that young, rapidly progressing subjects will benefit from ALCAR treatment.

Acetylcarnitine↗

PubMed1995

Oral physostigmine in Alzheimer's disease: effects on norepinephrine and vasopressin in cerebrospinal fluid and plasma.

Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in persons with Alzheimer's disease (AD) the effects of an acute dose of physostigmine in patients receiving chronic physostigmine treatment on the activity of the cholinergically regulated noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated the effects of sustained release oral physostigmine on central and peripheral noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic saline infusion also were measured. NE concentrations in both CSF and plasma were significantly lower in the physostigmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affect the AVP response to hypertonic saline. Physostigmine appears to decrease both central and peripheral noradrenergic activity in AD.

Administration, Oral↗

PubMed1995

Vasopressin and galanin mRNAs coexist in the nucleus of the horizontal diagonal band: a novel site of vasopressin gene expression.

Vasopressin (VP) neurons have been identified in several brain regions where VP has been hypothesized to act as a neurotransmitter or neuromodulator. In many sites, VP is colocalized with the neuropeptide galanin (GAL). Here, using single in situ hybridization histochemistry, we have identified a novel group of neurons within the nucleus of the horizontal diagonal band of Broca (HDB) that express the VP gene and have assessed the distribution of these cells in adult male and female rats (90 days old, n = 7/group). VP mRNA-expressing neurons were scattered throughout the rostrocaudal extent of the HDB, and the number of VP neurons detected unilaterally ranged from 1 to 17 cells per 20 microns section. Using double in situ hybridization histochemistry on alternate sections, we have assessed the number of cells expressing VP and/or GAL mRNA in the diagonal band and have determined the extent of their colocalization. Approximately 50% of all VP-expressing neurons in the HDB coexpressed GAL mRNA, and 33% of GAL-expressing neurons in this region coexpressed VP mRNA. No sex differences were detected in the number of neurons expressing either VP or GAL mRNA or in the incidence of coexpression of VP and GAL mRNAs in this region. VP neurons in the HDB exhibited a low level of expression, and cellular VP mRNA content did not differ between male and female rats. However, sex differences were present in the bed nucleus of the stria terminalis (BNST) of these same rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effects of Alzheimer's disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine.

BACKGROUND: The resting cerebrospinal fluid (CSF) norepinephrine concentration is unchanged or even increased in patients with Alzheimer's disease (AD). These in vivo findings appear to be inconsistent with the post-mortem locus ceruleus neuronal loss that is reported in patients with AD. METHODS: The effects of AD and advanced age on central nervous system noradrenergic status were estimated by comparing CSF norepinephrine concentrations following the administration of yohimbine hydrochloride, clonidine hydrochloride, and placebo in outpatients with AD and older and young normal subjects. Levels of yohimbine, its metabolite 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, Excitement, and Anxiety items on the Brief Psychiatric Rating Scale. RESULTS: Yohimbine-induced increases of CSF norepinephrine concentrations were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepinephrine concentrations did not differ among groups. Behavioral arousal following the administration of yohimbine was greater in patients with AD than in the other groups. CONCLUSIONS: Central nervous system noradrenergic responsiveness is enhanced in normal older subjects, and this age effect is retained in patients with AD. Behavioral sensitivity to increased central nervous system noradrenergic activity is enhanced in patients with AD.

Adult↗

PubMed1995

The effects of normal aging on cortisol and adrenocorticotropin responses to hypertonic saline infusion.

To assess the effects of aging on hypothalamic-pituitary-adrenal (HPA) axis responsivity, we compared the plasma cortisol and adrenocorticotropin (ACTH) responses to hypertonic saline infusion between normal older and young human volunteers. We administered a 90 min hypertonic saline infusion (5% sodium chloride at 0.06 ml/kg/min) and a 90 min placebo infusion (0.9% sodium chloride at 0.06 ml/kg/min) to normal young subjects (n = 13, age = 29 +/- 2 years) and normal older subjects (n = 8, age = 63 +/- 3 years). Plasma cortisol, ACTH, osmolality and arginine vasopressin (AVP) were measured before and at 30 min intervals during the infusions. The rate of increase in plasma osmolality and AVP induced by hypertonic saline infusion was similar between groups. The plasma cortisol increase during hypertonic saline infusion was greater in normal older subjects than in young subjects (p = .03), but a stimulatory effect of hypertonic saline infusion on plasma ACTH was not apparent in either older or young subjects. These results suggest increased sensitivity with human aging to stimulation of cortisol release by hypertonic saline infusion at the adrenocortical level of the HPA axis.

Adrenocorticotropic Hormone↗

PubMed1995

Lack of cholinergic regulation of vasopressin and norepinephrine responses to hypertonic saline in humans.

In vitro studies in hypothalamic-pituitary explants in the rat have suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.

Adult↗