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Biomedical subjects

D M Bowden

Publications and source records attributed to D M Bowden.

At least 55 records · Page 3Linked to original sources
PubMed1984

Measures of alcohol damage in utero in the pigtailed macaque (Macaca nemestrina).

A non-human primate model for the fetal alcohol syndrome (FAS) has been developed in a pilot study on four pigtailed macaques (Macaca nemestrina) receiving ethanol once weekly from 40 days of gestation (2.5 g/kg for three moderate-dose monkeys and 4.1 g/kg for one high-dose monkey). Ethanol and acetaldehyde levels and indices of general health were monitored throughout pregnancy. One pregnancy ended in miscarriage. The three infants born at term were compared to control infants. The infant exposed to the higher ethanol dose showed phenotypic similarities to humans with FAS. Its brain was microcephalic and dysplastic; reflex, motor and cognitive development were retarded. One infant receiving the moderate dose had subtle brain abnormalities; it was hyperkinetic and showed developmental retardation on several behavioral measures. The other moderately dosed infant was normal. A larger study now in progress will comprise six groups of seven monkeys, each group being exposed to 0 (control), 0.3, 0.6, 1.2, 2.5 or 4.1 g/kg of ethanol once weekly throughout gestation. So far, 4.1 g/kg ethanol has been shown to be fetotoxic when given between 8 and 13 days of pregnancy.

Animals↗
PubMed1984

Aging.

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Aging↗
PubMed1983

Differential effects of dopaminergic agonists on food-reinforced operant behavior in the long-tailed macaque (Macaca fascicularis).

Dopaminergic involvement in the regulation of operant behavior was examined by monitoring responding after administration of different dopaminergic agonists. A chain schedule of reinforcement was used to classify the effects of these agonists in long-tailed macaques (Macaca fascicularis). The schedule included the following: (1) a 30-s time-out period; (2) a clock-cued 30-s period of differential reinforcement of zero-response rate; (3) a time-in period whose duration depended on response latency; (4) a 2-s reinforcement period in which applesauce was delivered. This cycling schedule maintained a low operant rate and was sensitive to both inhibition (decreases) and excitation (increases) of responding. IV injection of the dopaminergic agonists resulted in the following two basic effects: (1) d-amphetamine and amfonelic acid disrupted performance by response inhibition, which was shown not to be attributable to anorexia; (2) apomorphine and bromocriptine disrupted performance by response excitation. Both effects were reduced by pretreatment with trifluperidol, a dopaminergic antagonist. The results, indicating that dopaminergic systems mediate disruption of food-reinforced operant behavior by altering the frequency of responding, are interpreted in terms of the known neuropharmacological actions of the agonists.

Animals↗
PubMed1982

Fetal alcohol syndrome: a new primate model for binge drinking and its relevance to human ethanol teratogenesis.

Ethanol was administered nasogastrically to four gravid pigtailed macaques (Macaca nemestrina) weekly from 40 days after conception to term. Three animals received 2.5 gm/kg and one received 4.1 gm/kg per dose. One animal aborted after the first dose of 2.5 gm/kg ethanol. Serum ethanol and acetaldehyde were measured after each dose in the other three animals, who carried to term. After delivery the infants were assessed for growth, dysmorphic features, and neurologic and psychological development over six months and were compared with 10 age- and sex-matched controls. Complete autopsies with neuropathologic examinations were performed. The animal exposed to the high dose had neurologic, developmental, and facial anomalies similar to those seen in human fetal alcohol syndrome. One of the animals exposed to the more moderate dosage was similarly but less severely affected. The study demonstrates that a model for binge drinking and fetal alcohol syndrome can be developed in a primate. The model should be useful in exploring the mechanisms of teratogenesis and in determining the median effective dose for the production of the various anomalies seen in fetal alcohol syndrome.

Alcohol Drinking↗
PubMed1981

Catecholaminergic involvement in the biphasic effect of ADATN on temperature in mice.

A prodrug of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADHTN), 2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene (ADATN), was tested for activation of central dopaminergic receptors as measured by colonic temperature in mice. Intraperitoneal injections of ADATN (200 and 800 mumol/kg) produced hypothermia; and intermediate dose (400 mumol/kg) caused hyperthermia followed by hypothermia. A similar biphasic effect occurred with the one dose of ADHTN (800 mumol/kg) tested. Pretreatments with catecholaminergic antagonists were used to characterize the biphasic effect of the intermediate dose of ADATN. The hyperthermic phase depended on the release of endogenous catecholamines which activated alpha- and beta-adrenergic receptors. The hypothermic phase was mediated by a direct activation of dopaminergic receptors. The results are discussed in terms of the pharmacodynamics of a prodrug, the actions of ADHTN, and the known effects of indirect- and direct-acting catecholaminergic agonists on temperature. The involvement of different catecholaminergic systems in the effects of ADATN may limit its usefulness as a dopaminergic prodrug.

Animals↗
PubMed1981

3-O-,4-O-diacetylisoproterenol and 3-O-,4-O-dibenzoylisoproterenol: hypothermic effects in mice and the involvement of beta-adrenergic receptors.

Prodrugs of isoproterenol, 3-O-,4-O-diacetylisoproterenol (DAI) and 3-O-,4-O-dibenzoylisoproterenol (DBI), were tested for effects on colonic temperature in mice. Intraperitoneal injections of DAI or DBI (20, 50 and 125 mumol/kg) produced a dose-related hypothermia. Isoproterenol (125 mumol/kg) and its metabolite, 3-O-methylisoproterenol (125 mumol/kg), caused hypothermia of a lesser intensity. The involvement of beta-adrenergic receptors in the hypothermic effect of DAI (50 mumol/kg) was established by pretreatments with propranolol and sotalol. The results are discussed in terms of the pharmacodynamics of prodrugs, the pharmacokinetics and mechanism of action of isoproterenol, and the possible role of beta-receptors in temperature regulation. DAI and DBI may be useful as prodrugs for the activation of central beta-receptors.

Animals↗
PubMed1981

A chronic stereotaxic guide-tube platform for intracranial infections in macaques.

Intracranial injection is a valuable method for testing the effects of pharmacologic agents on the central nervous system or specific areas of the brain with minimal peripheral effects. Improved apparatus and techniques have made it possible to treat the same site repeatedly over extended periods of time in unrestrained subjects. Methods are described for the construction and implantation of a durable platform that assures stereotaxic accuracy of intracranial injections for up to two years. The design and use of two kinds of injection cannula for intracerebroventricular and intracerebral injections of one or a few microliters are described in detail. The apparatus and methods have been used in studies of large number of rhesus, longtailed, and pigtailed macaques over a period of several years. The influence of species characteristics and skull growth on the effectiveness of the techniques is discussed.

Animals↗
PubMed1978

An autoradiographic, semistereotaxic mapping of major projections from locus coeruleus and adjacent nuclei in Macaca mulatta.

The autoradiographic method was used to trace projections from the monkey locus coeruleus (LC) and adjacent nuclei (nn. parabrachiales, n. tractus mesencephalicus nervus trigemini, substantia grisea centralis). Pathways attributed to LC are presented diagrammatically in a set of 26 coronal sections. They include a descending pathway along the tractus tegmentalis centralis, a caudal pathway entering the corpus medullaris cerebellaris via the lateral wall and roof of ventriculus quartus, and an ascending pathway along the tractus tegmentalis centralis giving off branches to the commissura posterior, tractus habenulo-interpeduncularis, centrum medianum and n. ventralis posteromedialis thalami, fasciculus lenticularis, lamina medullaris thalami lateralis, capsula interna, commissura supraoptica dorsalis, tractus supraoptico-hypophyseus, stria terminalis, laminae medullaris interna and medialis and pars interna of globus pallidus, corpus subfornicale, capsula externa, stria longitudinalis, cingulum, and gyrus rectus. A contribution to the branches entering n. ventralis posteromedialis thalami and the commissura supraoptica dorsalis was attributed to the nn. parabrachiaels. Axons entering trigeminal structures via the tractus mesencephalicus nervus trigemini were attributed to labeling of cells in the nucleus of that tract. Terminal areas attributed to labeling of LC axons were evident in decreasing order of density in the bed nucleus of stria terminalis, substantia innominata, nn. amygdalae anterior, centralis and basalis (dorsal portion), nn. paraventricularis, supraopticus and dorsomedialis hypothalami, and n. antero-ventralis thalami.

Animals↗
PubMed1977

Malignant lymphoma in a squirrel monkey (Saimiri sciureus).

A juvenile male Saimiri sciureus died of a tumor diagnosed as a histiocytic type of malignant lymphoma. The neoplasm presented as a thoracic mass occupying the posterior mediastinum and infiltrating the contiguous structures without involving distant nodes, the liver or spleen. The tumor tissue consisted of sheets or poorly defined clusters of fairly large cells with a vesicular nucleus and a variably abundant cytoplasm. The tumor cells were laid out in a poorly developed stroma of fine argyrophilic fibers. This is the first report of a spontaneous malignant lymphoma in a primate of this species. The speculation is put forth that the reported tumor is probably the first known example of the long sought after correlate of squirrel monkeys to Burkitt lymphoma in man.

Animals↗
PubMed1975

Locus ceruleus in rhesus monkey (Macaca mulatta): a combined histochemical fluorescence, Nissl and silver study.

The locus ceruleus (LC) of the rhesus monkey (Macaca mulatta) was investigated using the histochemical fluorescence method and Nissl and ammoniacal silver stains. Caudally, a few fluorescent cells were observed in the lateral wall of the ventriculus quartus near the velum medullaris superior. Rostrally, the fluorescent cells were compactly clustered and reached their greatest density medial and, to a lesser extent, lateral to the tractus mesencephalicus n. trigemini at the level of the decussation of the nervus trochlearis. In the most rostral plane, fluorescent cells were more diffusely scattered ventral and medial to the pedunculus cerebellaris superior with a few cells situated near the nervus trochlearis. Nissl staining of tissue previously used for histochemical fluorescence showed that fluorescent cells were largely found in a region labelled LC in two rhesus monkey brain atlases and erroneously labelled nucleus tractus mesencephalicus n. trigemini in one brain atlas. Ammoniacal silver staining resulted in a dense accumulation of silver granules in the cells found to display a positive reaction for monoamines. The silver stains therefore offer an alternative to the histochemical fluorescence method for identifying the monoamine-containing LC neurons.

Ammonia↗
PubMed1975

Primate drinking system as defined by electrical stimulation of the brain (ESB).

Four rhesus monkeys were examined by ESB for drinking sites in structures that had been previously demonstrated to support drinking behavior. Three yielded a significantly greater proportion of drinking sites than expected from the earlier study, and one yielded significantly less. As the exploration proceeded, the proportion of sites yielding drinking greatly increased in the drinkers and decreased in the nondrinker, and the ratio of stimulus-bound to nonstimulus-bound drinking sites increased in the drinkers but decreased in the nondrinker. Orienting responses decreased in both drinker and nondrinker as exploration proceeded. Two sites that had reliably supported drinking in the restraint chair failed to do so when telestimulated in a free environment, but instead yielded turning, walking, and climbing behavior. The results suggest that ESB-elicited drinking is determined by stimulation of several overlapping neural systems. These probably include ascending dopaminergic and cholinergic systems which are relatively thirst specific, and a nonspecific, cholinergic component of the reticular activating system which triggers the animal to execute a prepotent response which is specific to a given animal with a given history of stimulation under particular enviromental constraints. The learning of stimulus bound drinking is proposed to have its neural locus within the system which mediates the prepotent response, rather than in a thirst system or general activation system.

Animals↗