Biomedical subjects

D E Schmidt

Publications and source records attributed to D E Schmidt.

At least 19 recordsLinked to original sources

PubMed2001

Endogenous morphine and codeine. Possible role as endogenous anticonvulsants.

Exogenously administered morphine can have both convulsive or anticonvulsive effects, depending on the dose and species. The levels of the endogenous opiate alkaloids morphine and codeine were significantly elevated in specific rat brain regions by the convulsive drug, pentylenetetrazole, as well as by the anticonvulsant drugs, carbamazepine and phenytoin. Morphine and codeine levels in peripheral tissues (heart, lung, spleen and adrenal) were unaffected by these drugs. Maximal increases in morphine levels were seen in the hypothalamus and striatum (2-10-fold), while lesser increases occurred in the midbrain and brain stem (2-4-fold). Codeine levels were also markedly increased in hypothalamus (5-10 fold), In contrast to morphine, codeine levels were also increased in the hippocampus (2-10-fold), but were unchanged in the striatum. These studies suggest that the endogenous alkaloids morphine and codeine are involved in the modulation of convulsions and that morphine and/or codeine may act as an endogenous anticonvulsant.

Animals↗

PubMed2001

Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns.

A novel high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS) method is described for the determination of vancomycin in serum and urine. After the addition of internal standard (teicoplanin), serum and urine samples were directly injected onto an HPLC system consisting of an extraction column and dual analytical columns. The columns are plumbed through two switching valves. A six-port valve directs extraction column effluent either to waste or to an analytical column. A ten-port valve simultaneously permits equilibration of one analytical column while the other is used for sample analysis. Thus, off-line analytical column equilibration time does not require mass spectrometer time, freeing the detector for increased sample throughput. The on-line sample extraction step takes 15 seconds followed by gradient chromatography taking another 90 seconds. Having minimal sample pretreatment the method is both simple and fast. This system has been used to successfully develop a validated positive-ion electrospray bioanalytical method for the quantitation of vancomycin. Detection of vancomycin was accurate and precise, with a limit of detection of 1 ng/mL in serum and urine. The calibration curves for vancomycin in rat, dog and primate were linear in a concentration range of 0.001-10 microg/mL for serum and urine. This method has been successfully applied to determine the concentration of vancomycin in rat, dog and primate serum and urine samples from pharmacokinetic and urinary excretion studies.

Animals↗

PubMed2000

Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects.

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

Adolescent↗

PubMed1999

Salt-induced immobilization of affinity ligands onto epoxide-activated supports.

The immobilization of affinity ligands onto epoxy-activated stationary phases is enhanced at high concentrations of certain salts, such as ammonium sulfate and potassium phosphate. This enhancement is thought to occur because of a salt-induced hydrophobic interaction between the affinity ligand and the surface of the stationary phase. The increase in concentration of the affinity ligand near the reactive epoxy groups leads to an increase in the rate of reaction between the nucleophilic groups on the affinity ligand and the epoxide. The salt-induced enhancement is applicable to proteins and nucleotides at neutral pH and to small affinity ligands at elevated pH. In most cases, the hydrolysis of the epoxy groups does not limit the amount of affinity ligand immobilized. This review discusses the use of high salt concentrations to immobilize proteins, oligonucleotides and peptides to epoxy-activated silica and polymer supports. These modified supports can be used in affinity applications such as affinity chromatography or immunoassays.

Chromatography, Affinity↗

PubMed1999

Biogenic amine activity in response to fluoxetine and desipramine in differentially reared rhesus monkeys.

BACKGROUND: It has been hypothesized that adverse early experience may be a mechanism by which children become vulnerable to later psychopathology via alteration of neurochemical or hormonal systems associated with such disorders. Such effects may in turn affect later responses to pharmacologic agents that act on these systems. METHODS: In this study, 18 mother-reared (MR) and 18 peer-reared (PR) rhesus monkeys experienced six 1-week separations from cagemates interspersed with 1-week reunions, while housed in like-reared groups of 3. Within rearing groups, equal numbers of animals received either fluoxetine (2 mg/kg), desipramine (5 mg/kg) or placebo delivered daily beginning 4 weeks before the first separation. Levels of norepinephrine (NE), the NE metabolite MHPG, the dopamine metabolites DOPAC and HVA, and the serotonin metabolite 5HIAA were measured in CSF samples collected approximately every 2 to 3 weeks during these procedures. RESULTS: Following treatment, DMI increased NE and decreased MHPG in the DMI-treated groups, while 5HIAA was decreased in the fluoxetine-treated groups following treatment. The increase in NE was followed by a sharp decline over the course of treatment, which was accompanied by an increase in MHPG. The rearing groups did not show a differential response to the drug treatments, and the separation manipulation itself had few effects. The mother-reared group showed higher levels of NE and DOPAC over all samples and higher levels of HVA in most samples. CONCLUSIONS: These rearing effects on biogenic amine activity were observed even in the presence of pharmacologic treatments that effectively altered the activity of these systems, and are consistent with previous findings from the same subject. The higher NE values observed in mother-reared infants over separations and reunions may have been due to higher basal levels of NE than peer-reared monkeys or to greater responsiveness to the stress of repeated social disruption or both. These findings agree with other primate studies showing that rearing differences persist beyond the infancy period and add to growing evidence of the important influence of the early social environment on neurobiologic development in primates.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Fractional oxidation of chylomicron-derived oleate is greater than that of palmitate in healthy adults fed frequent small meals.

Differences in oxidation of individual dietary fatty acids could contribute to the effect of dietary fat composition on risk factors for non-insulin-dependent diabetes mellitus and cardiovascular disease. Using a novel stable isotope technique, we compared fractional oxidation of chylomicron-derived oleate and palmitate in 10 healthy adults in a crossover study. 1-(13)C-labeled oleate or palmitate was emulsified into a eucaloric formula diet administered each 20 min for 7 h to produce a plateau in excretion of (13)C label in breath CO(2). Unlabeled oleate and palmitate each provided 16% of dietary energy, and other fatty acids provided 8% of energy. Total dietary fat was 40% of energy, carbohydrate was 46%, and protein was 14%. Diet without tracer was fed for 2 h before beginning tracer administration to establish a baseline fed state. Relative oxidation of oleate versus palmitate was defined as fractional oxidation of oleate divided by fractional oxidation of palmitate. Relative oxidation averaged 1.21 (99.5% confidence interval = 1.03;-1.39), indicating that fractional oxidation of oleate was significantly greater than that of palmitate.

Adult↗

PubMed1999

Characterization of (S)-des-4-amino-3-[125I]iodozacopride ([125I]DAIZAC), a selective high-affinity radioligand for 5-hydroxytryptamine3 receptors.

The 5-hydroxytryptamine(HT)3 receptor subtype is present in the central nervous system (CNS) in low abundance, and few selective radiolabeled antagonists with high specific activity are available to study these sites. DAIZAC [desamino-3-iodo-(S)-zacopride; (S)-5-chloro-3-iodo-2-methoxy-N-(1-azobicyclo-[2.2. 2]oct-3-yl)benzamide] is a compound with high affinity and selectivity for the 5-HT3 receptor. Scatchard analysis of specific binding to NCB-20 cell membranes gave a Bmax of 340 +/- 58 fmol/mg protein and a KD of 0.14 +/- 0.03 nM, which is in agreement with the value previously reported in rat brain (KD = 0.15 nM). Nonspecific binding of [125I]DAIZAC in NCB-20 cells was <1% of total binding at the KD for DAIZAC compared with 17% in the rat brain preparation. Unlabeled DAIZAC (10 microM) showed minimal ability to displace binding of radiolabeled ligands selected for their affinities for other CNS receptor and uptake carrier binding sites. The discrimination ratio of DAIZAC for the 5-HT3 receptor over the M1 muscarinic binding site, the non-5-HT3 site at which it was most potent, was >2800. Serotonergic antagonists at every other known CNS serotonergic binding sites (3-30 microM) were ineffective in displacing [125I]DAIZAC binding in rat brain membranes. Similarly, antagonists (3-30 microM) for other nonserotonergic receptors and uptake sites were ineffective in displacing [125I]DAIZAC binding. Autoradiographic studies showed highest specific binding in area postrema and nucleus solitarius, with intermediate levels of binding in entorhinal cortex and hippocampus. DAIZAC inhibited 5-HT3 receptor-mediated inward cation current in NCB-20 cells with an IC50 of 0.24 nM. [125I]DAIZAC is a potent and highly selective ligand for in vitro studies of the 5-HT3 receptor.

Animals↗

PubMed1998

Protein affinity map of chemical space.

Affinity fingerprinting is a quantitative method for mapping chemical space based on binding preferences of compounds for a reference panel of proteins. An effective reference panel of <20 proteins can be empirically selected which shows differential interaction with nearly all compounds. By using this map to iteratively sample the chemical space, identification of active ligands from a library of 30,000 candidate compounds has been accomplished for a wide spectrum of specific protein targets. In each case, <200 compounds were directly assayed against the target. Further, analysis of the fingerprint database suggests a strategy for effective selection of affinity chromatography ligands and scaffolds for combinatorial chemistry. With such a system, the large numbers of potential therapeutic targets emerging from genome research can be categorized according to ligand binding properties, complementing sequence based classification.

Chromatography, Affinity↗

PubMed1998

Otolaryngological manifestations of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is one of the uniformly fatal spongiform encephalopathies that is characterized clinically by an unrelenting progression of myoclonus, dementia, and ataxia. Since many of these patients will develop cerebellar abnormalities, some may present to the otolaryngologist with dizziness. Hearing loss, however, to our knowledge, has not been reported. We describe a patient with CJD who presented with hearing loss and vague symptoms of imbalance, and whose disease progressed rapidly and fatally despite an extensive initial workup that was otherwise unrevealing. A review and discussion of the otolaryngological manifestations of CJD is presented. The otolaryngologist should be aware that CJD can present with otolaryngological manifestations, and with proper diagnosis extensive workups may be avoided.

Aged↗

PubMed1998

Characterization of desamino-5-[125I]iodo-3-methoxy-zacopride ([125I]MIZAC) binding to 5-HT3 receptors in the rat brain.

1. Antagonists at 5-HT3 receptors have shown activity in animal models of mental illness, however, few radiolabeled 5-HT3 ligands are available for preclinical studies. MIZAC, an analogue of the selective 5-HT3 antagonist, zacopride, binds with high affinity (1.3-1.5 nM) to CNS 5-HT3 sites. The authors report here the selectivity of MIZAC for these sites in rat brain homogenates. 2. Ninety-seven percent of total specific binding of [125I]MIZAC (0.1 nM) of was displaced by bemesetron (3 microM), a selective 5-HT3 antagonist. Competition studies using ligands with known affinities for 5-HT3 sites give a high correlation with reported pKi values (r2 0.98). Bemesetron displaceable binding has a regional distribution consistent with that of the 5-HT3 receptor, i.e. highest in cortex and hippocampus, and lowest in striatum and cerebellum. 3. Potent antagonists present at concentrations sufficient to occupy 95% of other 5-HT receptor populations (1A, 1B, 1D, 2A, 2B, 2C, 5A, 5B, 6, and 7) showed minimal ability to displace [125I]MIZAC binding (3 nM). Specificity studies using radioligand binding assays selective for 5-HT4, 5-HT6, and 5-HT7 receptors, and for binding sites of other neurotransmitters indicate a high degree of selectivity of [125I]MIZAC for the 5-HT3 receptor. 4. [125I]MIZAC binds to an apparent low affinity (benzac) site having a unique pharmacology. Low affinity binding was displaceable by benztropine, but not by other muscarinic agents nor inhibitors of dopamine uptake. The regional distribution of the low affinity site differed markedly from that of the high affinity site. The apparent affinity of [125I]MIZAC for the benzac site is two orders of magnitude lower than for the 5-HT3 receptor. Given its high selectivity for 5-HT3 binding sites, [125I]MIZAC appears to be a promising ligand for labeling 5-HT3 receptors in vitro and in vivo.

Animals↗

PubMed1998

Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain.

This report present evidence that the immunostimulant drug levamisole, (-)-(S)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b] thiazole monohydrochloride, produced a significant elevation of endogeneous morphine and codeine levels in brain regions and peripheral organs and attenuated the effects of naltrexone-induced withdrawal in morphine-addicted rats. Levamisole also significantly altered the metabolism of norepinephrine, dopamine, and serotonin in specific brain regions. These results suggest that levamisole's attenuation of opiate withdrawal may be related to its ability to increase endogeneous opiate alkaloid levels and/or to alter central monoaminergic function. Levamisole does not have significant affinity for opiate receptors. These results raise the intriguing possibility that agents such as levamisole, which elevate the levels of the endogenous opiate alkaloids, might be useful for treating narcotic withdrawal. The mechanism for the immunostimulatory properties of agents such as levamisole and muramyl dipeptide (MDP) have not been established. We suggest that the ability of MDP and levamisole to increase endogenous opiate alkaloids may be related to their immunostimulatory properties.

Adjuvants, Immunologic↗

PubMed1998

Lack of beta adrenoceptor desensitization in brain following the dual noradrenaline and serotonin reuptake inhibitor venlafaxine.

Venlafaxine, a dual amine reuptake inhibitor, was utilized to delineate the role of the individual aminergic components of the 'serotonin/noradrenaline link' in modifying receptor-linked second messenger cascades. Venlafaxine (20 mg/kg i.p. bid for 10 days) failed to alter in normal animals either the density of beta adrenoceptors or the response of the beta adrenoceptor-coupled adenylate cyclase system to noradrenaline but significantly decreased the cyclic AMP response to noradrenaline in the brain of rats with selective depletion of brain serotonin by p-chlorophenylalanine. The studies provide evidence for a cross-talk between noradrenergic and serotonergic receptor cascades at the level of mechanisms involved in the desensitization of the beta adrenoceptor-coupled adenylate cyclase system.

Adenylyl Cyclases↗

PubMed1998

Synthesis and 5-HT-3 receptor binding of 2- and 3-(halo)alkoxyl substituted (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chlorobenzamides as potential radioligands.

In an effort to develop selective, high-affinity radioligands for the 5-HT-3 receptor, a series of homologues of 5-chloro-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (2b) was prepared in which individual methoxy groups were replaced by ethoxyl, (2-fluoroethoxyl), allyloxyl, propargyloxyl, or (3-iodoallyl)oxyl groups. Affinities for the 5-HT-3 receptor were determined by displacement of the binding of [125I]MIZAC (2a), a selective 5-HT-3 receptor antagonist radioligand, in rat brain homogenates. The 3-substituted homologues were more potent than the lead compound, 2b. The homologue having the largest 3-substituent, i.e., E-(S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-3-(3-iodo-2-propenyl)oxy- 2-methoxybenzamide (3b, THIZAC), had one of the highest affinities, Ki 0.08 nM. The 2-substituted homologues were equipotent with 2b, having Ki 0.2-0.3 nM, regardless of the size of the substituent. The corresponding iodoallyl derivative, E-(S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-(3-iodo-2-propenyl)oxy- 3-methoxybenzamide (4, LIZAC), displayed a Ki of 0.29 nM. Saturation binding of [125I]-4 gave a KD of 0.31 +/- 0.04 nM and a Bmax of 2.36 +/- 0.10 fmol/mg of entorhinal cortex. In vivo biodistribution of [125I]-4 in the rat brain showed increased accumulation in hippocampus relative to that in cerebellum. Both the high-affinity ligands [125I]-3b and [125I]-4 are potentially useful radioligands for studying the 5-HT-3 receptor.

Animals↗

PubMed1997

The behavioral neurobiology of self-injurious behavior in rhesus monkeys. Current concepts and relations to impulsive behavior in humans.

The objective of this report is to critically review past reports and present new data on the psychobiology of self-injurious behavior (SIB) and/or "risky" or "impulsive" behavior in primates (human and nonhuman). One aim was to reexamine how early social deprivation and neurobiological changes caused by deprivation might contribute to SIB in monkeys, and how the causes of SIB in monkeys might inform us about the psychobiology of suicide in humans. A second aim was to examine the evidence that social deprivation in monkeys produces reductions in brain 5-HT system function that are causal or coincident factors associated with self-injurious or impulsive behavior. Prior studies and new data indicate that the environmental causes of SIB and unusual aggression in rhesus monkeys do not produce reductions in brain 5-HT system activity and that experimental production of low levels of brain 5-HT system activity does not reliably promote either SIB or unusual other-directed aggression in monkeys. A third and final aim was to suggest that in severe cases of environmentally induced SIB and/or aggression in monkeys, having relatively high or low levels of 5-HT system activity may not be related to ongoing behavior because the 5-HT system may not interact with other neurotransmitter systems in the usual way. Overall, the contention is that primates exhibiting SIB and unusual aggression may have altered 5-HT system function, but this may be but one aspect of a more profound disorganization of brain function involving many neurohormonal and transmitter systems. Contemporary theorizing and experimentation tends to be restricted to the idea that altered function in one key system might be the cause of a specific form of psychopathology. In the future, research examining the probable change interactions of neurotransmitter and neuroendocrine systems as underlying causes of behavioral disorders should have a high priority.

Animals↗

PubMed1997

Attenuation of 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity by deprenyl in organotypic canine substantia nigra cultures.

Systemic administration of MPTP to experimental animals induces neurodegeneration of dopaminergic neurons in the central nervous system. MPTP crosses the blood-brain barrier where it is taken up by astrocytes and converted to MPP+ by monamine oxidase-B (MAO-B). Subsequently, MPP+ is selectively taken up by dopaminergic neurons upon which it exerts intracellular neurotoxic effects. Systemic administration of the selective MAO-B inhibitor deprenyl prevents the conversion of MPTP to MPP+ and by this mechanism is able to protect against MPTP neurotoxicity. Deprenyl has also been reported to exert neuroprotective effects that are independent of its MAO-B inhibitory properties, but since MPP+ itself does not cross the blood-brain barrier it is difficult to directly study the MAO-B independent in vivo effects of MPP+ itself. One approach is to use organotypic tissue cultures of the canine substantia nigra (CSN) which permit administration of precise concentrations of pharmacological agents directly to mature, well-developed and metabolically active dopaminergic neurons. These neurons as well as other components of the cultures exhibit morphological and biochemical characteristics identical to their in vivo counterparts. This study was undertaken to evaluate the neuroprotective effects of deprenyl in MPP(+)-treated cultures by measuring changes in the levels of HVA as an indicator of dopamine release and metabolism by dopaminergic neurons and to correlate this indication of dopaminergic function with morphological evidence of survival or loss of dopaminergic neurons in mature CSN cultures. Mature CSN cultures, at 44 days in vitro (DIV), were exposed to either MPP+ alone, deprenyl alone or simultaneously to both deprenyl and MPP+ or to MPP+ following 4 day pretreatment with deprenyl. Exposure to MPP+ alone caused significant reduction in HVA levels, evidence of widespread injury and ultimate disappearance of large neurons in the cultures. These effects were attenuated by simultaneous exposure to MPP+ and deprenyl and the destructive effects of MPP+ appeared to be prevented by pretreatment with deprenyl. Thus the neuroprotective effects of deprenyl on MPP(+)-induced reduction of HVA levels in living cultures appears similar to the effects of deprenyl on dopamine levels and tyrosine hydroxylase activity reported by others in cultures previously exposed to deprenyl and MPP+. These studies also confirm that the neuroprotective effects of deprenyl against MPP+ in dopaminergic neurons are, at least in part, independent of deprenyl's inhibition of MAO-B.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1997

Elevated plasma gamma-aminobutyric acid (GABA) levels in individuals with either Prader-Willi syndrome or Angelman syndrome.

Plasma gamma-aminobutyric acid (GABA) levels were measured in 14 subjects with Prader-Willi syndrome, 9 subjects with Angelman syndrome, and matched control subjects. Mean levels in both patient groups were 2 to 3 times higher than in nonretarded moderately obese or retarded nonobese control subjects. Levels in each patient group differed significantly from both control groups. Neither the two patient groups nor the two control groups differed. GABA levels seemed unrelated to genetic status (chromosome 15 deletion or disomy). These preliminary findings of elevated plasma GABA levels possibly represent a compensatory increase in presynaptic GABA release in response to hyposensitivity of a subset of GABA receptors and could produce increased postsynaptic activation of other normal GABA receptor subtypes, resulting in complex alterations of GABAergic function throughout the brain.

Adolescent↗

PubMed1997

Synthesis and radiolabeling of (S)-4-amino-5-iodo-2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide, the active enantiomer of [125I]iodozacopride, and re-evaluation of its 5-HT3 receptor affinity.

We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)-iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to that obtained from (S)-3-amino-quinuclidine and 4-amino-2-methoxybenzoic acid via its corresponding 1-imidazole derivative. Radioiodination to produce (S)-[125I]iodozacopride was accomplished by treatment of deschloro-(S)-zacopride with 5 mCi sodium 125iodide and chloramine-T in hydrochloric acid. Purification of the reaction products using an HPLC system capable of detecting chlorinated side-products revealed a mixture of 2.1 mCi (1.3 nmol) (S)-[125I]iodozacopride and (S)-zacopride (1.5 nmol). Saturation analysis of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated KD of 1.10 +/- 0.07 nM. As anticipated, this is approximately half the KD reported for binding of racemic [125I]iodozacopride, and differs from the previously reported value by an order of magnitude. Analysis of the apparent binding affinity of a 1:1 mixture of (S)-[125I]iodozacopride and (S)-zacopride suggests that the previous result may have been confounded by contamination of the product with unlabeled (S)-zacopride. Competition analysis of the displacement of (S)-[125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)-zacopride gave Ki values of 0.95 and 0.21 nM, respectively.

Aminosalicylic Acid↗

PubMed1996

Rearing experience and biogenic amine activity in infant rhesus monkeys.

In this report we present evidence that early social experience influences aspects of the function of brain biogenic amine systems, most notably the noradrenergic system. Biogenic amine activity was studied in mother- vs. peer-reared monkey infants over the first 6 months of life and in response to two housing transitions. Norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebrospinal fluid (CSF) were measured. Peer-reared monkeys showed significantly higher CSF levels of norepinephrine and MHPG than mother-reared animals over early development, but showed an attentuated NE response to separation and group formation compared to mother-reared animals. Peer-reared monkeys showed a greater developmental decline in 5-HIAA levels than mother-reared monkeys. There were no rearing effects for DOPAC or HVA over early development; however, peer-reared monkeys showed significantly lower HVA and DOPAC concentrations at 6-8 months of age. The results add to evidence for the influence of primate mothers on the psychobiological development of central nervous system neurotransmitter systems in their infants, and suggest that the noradrenergic system is among the more sensitive of these to early experience.

Aging↗