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Biomedical subjects

G L Brammer

Publications and source records attributed to G L Brammer.

At least 19 recordsLinked to original sources
PubMed1992

Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences.

We examined the effects of gender, age, weight, length, body shape (ectomorphy), and matrilineal influences on cisternal cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and homovanillic acid (HVA) in 78 socially living adult and adolescent vervet monkeys. CSF 5-HIAA and the 5-HIAA:HVA ratio were higher (by 27% and 18%, respectively) in females. In both sexes, CSF 5-HIAA and the 5-HIAA:HVA ratio increased with age. Neither weight nor length were independently related to CSF 5-HIAA or HVA; however, shape correlated with CSF 5-HIAA and HVA in males (higher in thin, long subjects). Male offspring had CSF 5-HIAA concentrations and 5-HIAA:HVA ratios that were significantly closer to their mothers than did age-matched, maternally unrelated males. Repeated measures of CSF 5-HIAA and HVA in another 22 males living in unvarying settings showed that individual differences in these measures persisted over time. The data underscore the impact of gender, age, and matrilineal relationships on individual differences in CSF monoamine metabolites and highlight the importance of controlling for age and gender in neuropharmacological investigations of clinical populations.

Aging↗
PubMed1991

Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys.

In a counter-balanced, cross-over study, we examined the contributions of serotonergic systems to the acquisition of social dominance in adult male vervet monkeys. Subjects were members of 12 social groups, each containing 3 adult males, at least 3 adult females, and their offspring. Animals were observed in 5 intervals including a first baseline, a first experimental, a second baseline, a second experimental, and a third baseline period. At the end of the first baseline period, the dominant male was removed from each group. In each group, one of the two remaining subordinate males was selected at random for treatment and during the first experimental period, 6 of the 12 treated males received drugs that enhanced serotonergic activity (3 were given tryptophan 40 mg/kg/day and 3 fluoxetine 2 mg/kg/day). The other 6 treated males received drugs that reduced serotonergic function (3 were given fenfluramine 2 mg/kg/day and 3 cyproheptadine 60 micrograms/kg/day). At the end of the first experimental period, the original dominant male was returned to his group and the second baseline period began. In all instances, the originally dominant male regained his dominant position. The second experimental period began with the dominant male again being removed and, the 12 treated males were given the treatment they had not received in the first experimental period. At the start of the third 12-week baseline period, the original dominant male was returned to his group and resumed his dominant status. When the 12 treated subjects received tryptophan or fluoxetine, they became dominant in all instances. When they received fenfluramine or cyproheptadine, their vehicle-treated cage mates became dominant. The sequence of the behavioral changes shown by the treated males as they acquired dominance status paralleled those seen in naturalistic conditions. These observations support the distinction between dominance and aggression and strongly suggest that when hierarchical relationships are uncertain, serotonergic mechanisms may mediate the behaviors which permit a male to attain high dominance status.

Aggression↗
PubMed1991

Fenfluramine effects on serotonergic measures in vervet monkeys.

Chronic fenfluramine treatment reduced whole blood serotonin and CSF 5-hydroxyindoleacetic acid, but increased aggressive and locomotor behavior, in adult male vervet monkeys (Cercopithecus aethiops sabaeus). Following a drug-free washout period to monitor the drug recovery course, we initiated a second period of fenfluramine treatment in the same animals. When whole blood serotonin concentrations were reduced by about 40% from predrug baseline levels, we examined 11 cortical and subcortical brain regions for their content of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, norepinephrine, and dopamine. We observed correspondence between the reduction in whole blood serotonin and the reduction in brain 5-hydroxytryptamine. Similarly, there was a correspondence between the reduced 5-hydroxyindoleacetic acid levels observed in CSF and brain. No alterations were noted in the concentrations of norepinephrine or dopamine. These observations suggest that the behavioral effects observed in monkeys after chronic fenfluramine treatment result from reduced central serotonin.

Animals↗
PubMed1987

Vervet monkey (Cercopithecus aethiops sabaeus) whole blood serotonin level is determined by platelet uptake sites.

Whole blood serotonin levels in adult male vervet monkeys living in social groups are sensitive to the animals' social environment. The mechanisms that translate different behavioral and environmental cues into altered whole blood serotonin levels are unknown. In this study, we have measured platelet number, size, serotonin content, and serotonin uptake, as well as the serum concentrations of tryptophan, Mg+2 and Ca+2. Results showed that whole blood serotonin levels, platelet serotonin content, and the serotonin uptake parameter Vmax were stable within animals on repeated sampling. The whole blood serotonin level was highly positively associated with platelet serotonin content, and the platelet serotonin content was highly positively associated with Vmax. These findings suggested that whole blood serotonin levels were a function of the number of platelet uptake sites.

Animals↗
PubMed1987

Comparison of ketamine, physical restraint, halothane and pentobarbital: lack of influence on serotonergic measures in monkeys and rats.

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys (Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.

Animals↗
PubMed1987

Similarity of 5-HT2 receptor sites in dominant and subordinate vervet monkeys.

Pharmacological studies using serotonergic agents have revealed status-linked behavioral effects in dominant and subordinate vervet monkeys. A possible explanation for the greater drug response observed in dominant animals is that there is a CNS difference between dominant and subordinate animals. Such differences could exist at the level of serotonin receptor sites, membrane responsiveness, or interaction with other neurotransmitters. We have examined the specific 3H-ketanserin binding in various regions of vervet monkey brain to evaluate the hypothesis that dominant and subordinate vervet monkeys differ in CNS 5-HT2 receptor sites. No differences were found in the number or affinity of 3H-ketanserin binding sites between dominant and subordinate animals. Further, no differences were found in the displacement of 3H-ketanserin binding by the serotonin agonist quipazine. These results suggest the conclusion that differences at 5-HT2 binding sites do not account for status-linked differences in behavioral drug response in vervet monkeys and that other or additional mechanisms must underlie status-related drug response differences.

Animals↗
PubMed1986

Effects of chronic fenfluramine on blood serotonin, cerebrospinal fluid metabolites, and behavior in monkeys.

The effects of long term (70 days) fenfluramine treatment on selected physiological and behavioral measures were examined in four adult male vervet monkeys (Cercopithecus aethiops sabaeus). Relative to pretreatment baseline values, whole blood serotonin (WBS) and cerebrospinal fluid 5-hydroxyindole acetic acid (5-HIAA) were reduced, cerebrospinal fluid homovanillic acid (HVA) was unaltered, and aggressive and locomotor behavior were increased. Both physiological and behavioral effects were reversible: all measures returned to baseline values in the 35 day post-treatment period, with WBS resuming pretreatment values more rapidly than CSF 5-HIAA. At the relatively low doses (1-4 mg/kg/day) employed in the present study fenfluramine produced behavioral effects similar to those resulting from PCPA and opposite to those following tryptophan administration. Thus the behavioral effects of long-term fenfluramine may involve reductions in serotonergic transmission.

Aggression↗
PubMed1986

Resting cortisol levels and the emergence of dominant status among male vervet monkeys.

Resting serum cortisol was measured in adult male vervet monkeys (Cercopithicus aethiops sabaeus) in four different conditions: (1) among groups with unaltered group membership and established dominance hierarchies; (2) among groups from which the original dominant male had been removed and in which the remaining males competed for dominant status; (3) among newly formed groups of three unfamiliar males each of which had been the dominant male in his previous group; and (4) among groups from which a dominant male was temporarily separated and returned. In Condition 1, cortisol concentrations did not differ between dominant and subordinate males. The second condition showed that cortisol levels were highest among males who eventually emerged as the dominant male. In the third condition, however, cortisol levels did not differentiate eventually dominant from eventually subordinate males. In the last condition, cortisol levels were highest in the animals that became or remained dominant following reintroduction. These data indicate that cortisol concentration does not differ between dominant and subordinate males in stable groups and that cortisol rises during competition for dominance among familiar males.

Animals↗
PubMed1985

Dominant social status facilitates the behavioral effects of serotonergic agonists.

The effects of dominance rank on the behavioral responses to drugs that enhance central serotonergic function were examined in 45 adult male vervet monkeys living in 15 stable social groups. Each group contained 3 adult males, 3 adult females, and their immature offspring. Dominance rank was assessed by measuring success in intermale agonistic encounters. In every group one male was clearly the dominant, or alpha male, and the other two males were subordinate. Males from 5 groups received 3 doses of the serotonin reuptake inhibitor fluoxetine (0.5, 1.0 and 2.0 mg/kg/day); those from a second set of 5 groups received 3 doses of the receptor agonist quipazine (0.25, 0.50 and 1.0 mg/kg/day); those from a third set of 5 groups received the serotonin precursor tryptophan (10, 20 and 40 mg/kg/day). The 3 drug treatments produced strikingly similar behavioral effects. Each produced dose-dependent increases in approaching, grooming, resting and eating and decreases in locomoting, avoiding, being vigilant and being solitary. Dominant males were significantly more responsive behaviorally to all 3 drugs than were subordinate males: the increase or decrease in each behavioral measure was larger in dominant than in subordinate males. In combination with previous studies, these data suggest that dominant and subordinate males differ in the drug sensitivity of their serotonergic systems.

Age Factors↗
PubMed1985

Serum testosterone, male dominance, and aggression in captive groups of vervet monkeys (Cercopithecus aethiops sabaeus).

The relationship of serum testosterone concentration to male dominance rank and frequency of aggression was investigated in stable vervet monkey social groups, each containing two or three adult males, several adult females, and their offspring. Dominance relationships were determined by noting an animal's success in intermale aggressive encounters. A striking finding was the marked within-subject variation in testosterone concentration: 5- to 10-fold fluctuations were often observed on successive days. When all 15 groups were considered together, testosterone concentration was unrelated to dominance rank. Although mean testosterone concentration for all dominant males was higher than the mean for all subordinate males, this difference was not significant. In a subset of 4 groups, the rate of aggression initiated was significantly correlated with same-day testosterone in dominant but not in subordinate males.

Aggression↗
PubMed1984

Social and environmental influences on blood serotonin concentrations in monkeys.

Dominant male adult vervet monkeys have whole-blood serotonin concentrations approximately twice those of subordinate adult males. We examined the effects of spontaneous and induced changes in social status, temporary isolation from the social group, and membership in single male groups on whole-blood serotonin concentrations. We found that in male vervet monkeys, elevated blood serotonin concentration is a state-dependent consequence of active occupation of the dominant male social position, and we believe that a reinterpretation of the significance of hyperserotonemia in humans may be warranted.

Animals↗
PubMed1981

Neurotransmitter control of hypothalamic-pituitary-thyroid function in rats.

The possible roles of monoamine neurotransmitters in the regulation of the hypothalamic-pituitary-thyroid axis were examined in the rat. Rats were treated acutely and repeatedly with drugs which are presumed to alter neurotransmitter functional activity. These drugs include neurotransmitter precursors (tryptophan and L-DOPA), synthesis inhibitors (p-chlorophenylalanine and alpha-methyltyrosine), uptake inhibitors (desipramine and zimelidine) and lithium carbonate. The hormone levels measured were hypothalamic TRH and SLI content and serum TSH, T4 and T3. We conclude that augmented serotonergic or dopaminergic activity may inhibit TRH release, but that release from these inhibitions is not sufficient to stimulate TRH release. The release of TRH seems to be mediated by norepinephrine. Lithium treatment results in increased hypothalamic TRH.

Animals↗
PubMed1981

Short-term and repetitive administration of oral tryptophan in normal men. Effects on blood tryptophan, serotonin, and kynurenine concentrations.

Single and repetitive tryptophan loads were consumed by normal, adult male volunteers, and blood concentrations of tryptophan, serotonin, and kynurenine, their time courses, and their distributions within blood were measured. Repeated measures of basal and tryptophan-induced changes in tryptophan and serotonin blood concentrations were characteristic for individual subjects. Tryptophan dose-responsive increases in measured substances returned to basal levels within 24 hours after single tryptophan loads. However, cumulative increases in serotonin concentration in early-morning, predose blood samples were seen following repetitive daily tryptophan administration. Extra-platelet serotonin could be detected in blood samples taken after tryptophan loading and after repetitive daily tryptophan consumption but not in baseline samples taken before short-term loading. Neither platelet number nor size was altered by the loading procedures. Tryptophan loading produced lethargy and drowsiness within 30 minutes of ingestion under all loading conditions. Subjects with the slowest kynurenine response to tryptophan were most behaviorally affected.

Administration, Oral↗
PubMed1981

Peripheral correlates of serotonergically-influenced behaviors in vervet monkeys (Cercopithecus aethiops sabaeus).

The associations among twelve behaviors and three potential peripheral markers of central serotonergic activity were investigated in vervet monkeys (Cercopithecus aethiops sabaeus). The behaviors monitored included approach, heterogroom, rest, eat, avoid, be solitary, be vigilant, huddle, initiate aggress, receive aggress, and engage in sexual behavior. The biochemical parameters measured were whole blood serotonin, plasma free tryptophan, and plasma total tryptophan. Throughout the study period, intraindividual variability in both the behavioral and the biochemical measures was small, although there was substantial interindividual variability in both sets of measures. Free and total tryptophan correlated positively with approach, heterogroom, and eat, and inversely with avoid and be solitary. Whole blood serotonin correlated inversely with avoid and be solitary. These data are compatible with previously reported observations on the behavioral consequences of manipulating serotonergic systems in vervet monkeys and suggest that in normal, drug naive monkeys, free and total tryptophan are better correlates of the central serotonergic activity influencing behavior than is whole blood serotonin.

Animals↗
PubMed1981

Neonatal hormone treatment and maturation of the pineal noradrenergic system: hydrocortisone and thyroxine.

The circadian release of norepinephrine from nerve terminals in the pineal gland drives acetyl-CoA:serotonin N-acetyltransferase (NAT; EC 2.3.1.5) activity in the adult pineal from a daytime low to a nighttime high. In the newborn, enzyme activity is intermediate between the adult's daily extremes and has only a small circadian fluctuation. With age, these fluctuations increase in amplitude until the adult pattern is attained at about days 10-12. Treatment of neonates with thyroxine for the first 3 days of life accelerated, whereas administration of hydrocortisone acetate at birth retarded the developmental decline in daytime serotonin-N-acetyltransferase activity. Maximal differences in daytime enzyme activity of controls and thyroxine-treated animals were seen at day 4 and between controls and steroid-treated pups at day 8. Desipramine treatment increase NAT activity in 8-day-old animals; hydrocortisone-treated animals were least affected. Freshly cultured pineals from steroid-treated animals were more responsive to low, and less responsive to high, concentrations of norepinephrine than glands from thyroxine-treated or control animals. They were also less responsive to isoproterenol both in acute and 48-h organ culture. Pineals from hydrocortisone-treated animals in culture accumulated less exogeneous norepinephrine than glands from controls but released a greater fraction of their content on transfer to fresh medium. Normal and steroid-treated animals released the same fraction of their norepinephrine contents into the medium when reuptake was blocked by desipramine (DMI).

Acetyltransferases↗