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Biomedical subjects

W H Bridger

Publications and source records attributed to W H Bridger.

At least 19 recordsLinked to original sources
PubMed1992

Test-retest reliability of the prolactin and cortisol responses to D,L-fenfluramine challenge in disruptive behavior disorders.

We examined the intraindividual stability of plasma prolactin (PRL) and cortisol responses to D,L-fenfluramine challenges (1.0 mg/kg, p.o.), at a 1-week interval, in boys with disruptive behavior disorders. Two acute administrations of fenfluramine produced consistent and predictable effects on net prolactin responses (peak delta PRL, area under the curve delta PRL), but variable and unpredictable effects on net cortisol responses. The time course and magnitude of fenfluramine blood levels, not nor-fenfluramine, paralleled net PRL responses to fenfluramine. These data indicate that the PRL response to fenfluramine shows continuity within individuals over the course of 1 week, providing a reliable index to reflect the overall function of the serotonin system in the limbic-hypothalamus.

Arousal↗
PubMed1992

Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents.

Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression.

Adolescent↗
PubMed1991

Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder?

This study entailed the adoption of a well-established behavioral paradigm, spontaneous alternation, as a possible animal model for some of the symptoms observed in obsessive-compulsive disorder (OCD) in humans. Food-deprived rats were run in a T-maze in which both a black and a white goal box were equally baited with a small amount of chocolate milk. Each rat was given 7 trials every other day during which it was placed in the start box and allowed to make a choice. The mean number of choices until an alternation occurred was recorded. After a stable baseline of spontaneous alternation was achieved the effects of manipulating the serotonergic system were tested. Both the nonselective 5-HT agonist 5-MeODMT (1.25 mg/kg) and the more selective 5-HT1A agonist 8-OH-DPAT (2 mg/kg) disrupted spontaneous alternation. A course of chronic treatment (2 x 5 mg/kg for 21 days) with the selective 5-HT uptake blocking agent fluoxetine had a protective effect on the 5-MeODMT-induced disruption of spontaneous alternation behavior. Serotonergic manipulations of spontaneous alternation may be a simple animal model for the perseverative symptoms or indecisiveness seen in people diagnosed with OCD.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients.

Platelet imipramine binding was measured in 16 drug-free nondepressed patients (aged 20-61 years, mean +/- SD 35 +/- 8) suffering from obsessive-compulsive disorder (OCD) and in 16 sex-, race- and age-matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5-HT) uptake capacity, Vmax, was also measured in 15 of these patients and their matched controls. Vmax was significantly higher in the patients (309 +/- 149 pmol/10(9) cells/min) than in the controls (181 +/- 110). An increase in platelet 5-HT uptake supports the involvement of 5-HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder.

Adult↗
PubMed1989

Elevated platelet MAO is related to impulsivity in disruptive behavior disorders.

Platelet monoamine oxidase (MAO) activity was measured in 32 drug-free prepubertal boys with externalizing symptoms of disruptive behavior disorders and 47 boys with no DSM-III-R diagnoses, and correlated to questionnaire and laboratory performance measures of impulsivity. A subgroup of boys with high MAO activity exhibited significantly poorer performance (i.e., more impulsivity) than a subgroup of low MAO activity on laboratory tasks requiring response inhibition. High MAO patients were more impulsive than high MAO controls on some performance tasks and elevated platelet MAO was unrelated to personality questionnaire measures of impulsivity or to patient status. These data suggest that biological markers such as MAO activity may correlate better with performance than clinical questionnaire measures. Abnormally high platelet MAO activity may not be sufficient to produce externalizing symptoms in children, perhaps interacting with an underlying behavioral dimension of impulsivity.

Attention Deficit Disorder with Hyperactivity↗
PubMed1987

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Adolescent↗
PubMed1985

Place conditioning with morphine and phencyclidine: dose dependent effects.

In a place conditioning paradigm, rats were exposed to one of two distinctive environments following injection of drug or vehicle. Preference was measured under drug free conditions by allowing subjects free access to both settings and measuring where they spent more time. Comparisons were made between morphine and saline; PCP and saline; and one of several doses of morphine and a standard dose. Morphine was preferred over saline and, when compared to the reference dose, lower doses of morphine were less preferred and higher doses more preferred. PCP was never preferred over saline and under some conditions produced a conditioned place aversion. The ability to generate dose dependent effects with morphine should allow more sophisticated studies in which shifts in dose response curves are required.

Animals↗
PubMed1985

Electrodermal activity of undersocialized aggressive children: a pilot study.

Electrodermal activity of 11 children with conduct disorder (CD) and 11 normal children were compared during periods of rest, moderate tone and loud bell stimulation. The CD group was best differentiated from controls by lower reactivity to the first bell, while on tonic measures they showed normal values. The electrodermal profile of the CD children thus resembled that of adult sociopaths on phasic measures only. The possibility of using electrodermal measures for predicting outcome and for differential diagnosis is raised.

Acoustic Stimulation↗
PubMed1985

Biogenic amine alterations in limbic brain regions of muricidal rats.

Endogenous levels of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), dopamine, 3-4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in eight brain regions of muricidal (mouse killing) and non-muricidal rats. The regions studied were: the frontal cortex, caudate nucleus, septal area, hypothalamus, thalamus, amygdalae with pyriform cortex, anterior hippocampal formation, and brain stem. Serotonergic systems showed significant differences in discrete brain regions of muricidal rats as compared to those of non-muricidal rats. The differences were: significantly higher serotonin levels in the amygdalae and significantly higher 5-HIAA levels in the hippocampus of the muricidal rats. Serotonin levels were also higher in the hypothalamus of the muricidal rats, but the difference reached only borderline significance. Dopaminergic systems also showed significant differences in the septum of muricidal rats, where DOPAC levels were significantly lower than those of non-muricidal rats. The hippocampus of muricidal rats showed significantly higher dopamine levels. HVA levels in the hippocampus of muricidal rats were also higher but reached only borderline significance. These data suggest both central serotonergic and central dopaminergic involvements in rat muricidal behavior. The discrete brain regions which showed differences further suggest a limbic involvement.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Hormonal influences on seizure kindling: the effects of post-stimulation ACTH or cortisone injections.

Repeated application of brain stimulation can lead to a progressively augmenting electrical and behavioral response-- a phenomenon termed seizure kindling. In this experiment, stimulation was delivered once per day, and was followed by peripheral (intraperitoneal) administration of ACTH or cortisone. An intermediate or a high dose of either hormone (0.3 IU or 3.0 IU of ACTH/animal, 10 mg or 25 mg cortisone/animal) delayed the completion of kindling if administered shortly after each kindling stimulation. Lower doses (0.03 IU of ACTH or 2 mg of cortisone) had no significant effects. The high dose of ACTH or cortisone was no longer effective if administration was delayed more than 4 h after stimulation. Peripherally administered ACTH and cortisone can influence processes initiated by the brain stimulation which presumably underlie the augmentation of response to successive stimulations. This time-limited action is analogous to the effects of these hormones on memory consolidation.

Adrenocorticotropic Hormone↗
PubMed1981

L-Tryptophan's effects on mouse killing, feeding, drinking, locomotion, and brain serotonin.

Injections of the serotonin precursor l-tryptophan (25, 50, and 100 mg/kg IP), inhibited mouse killing behavior in rats, as indicated by a dose dependent increase in latencies to attack and kill mice. Tests in 24 hr food deprived rats revealed that feeding behavior was also significantly decreased by about 30% by tryptophan injections (50--100 mg/kg IP). Concomitant with the behavioral changes were increased levels of brain serotonin and its metabolite 5-hydroxyindoleacetic acid. Drinking, latencies to sniff mice, and ability to locomote on a rotating rod were not affected by l-tryptophan injections, although spontaneous activity in an open field was reliably reduced by 33% with a dose of 100 mg/kg. Thus, while the degree of selectivity for tryptophan's effects on behavior remains open to question, these findings are consistent with hypotheses of an inhibitory role for central serotonergic systems, particularly in mouse killing and feeding behaviors.

Aggression↗
PubMed1979

Manipulations of dietary tryptophan: effects on mouse killing and brain serotonin in the rat.

Maintaining rats on a tryptophan-free diet for 4--6 days induced mouse killing in non-killer rats, and significantly facilitated killing in killer rats, as indicated by shorter latencies to kill the mice. The killing responses were similar in topography to the natural killing responses. These changes in killing behavior did not appear to be due to generalized changes in irritability. The increased killing after maintenance on a tryptophan-free diet was accompanied by a 26% reduction in brain serotonin (5-HT) and a 29% reduction in brain 5-hydroxyindoleacetic acid (5-HIAA). When the tryptophan-free diet was supplemented with L-tryptophan (0.5 or 2%), brain 5-HT and 5-HIAA were increased above control levels, and the rat's killing response appeared normal both in terms of latency and topography, similar to that seen in control chow fed animals. While rats consumed less of the tryptophan-free and tryptophan supplemented diets, control subjects deprived of chow such that they lost as much weight as rats fed the tryptophan-free diet, did not show changes in killing behavior. These results are consistent with the hypothesis that central serotonergic systems exert inhibitory control over mouse killing behavior in rats.

Aggression↗
PubMed1979

A comparison of the effects of acute and subacute administration of beta-phenylethylamine and d-amphetamine on mouse killing behavior of rats.

beta-Phenylethylamine (PEA) is an endogenous amine that in some instances acts biochemically and behaviorally like amphetamine. In the present experiments, the effects of PEA on mouse killing by rats were compared and constrasted with the effects of d-amphetamine on this behavior. When given acutely to experienced mouse killing rats, PEA (16 and 32 mg/kg) inhibited killing in a direct dose dependent manner. This is similar to the dose dependent inhibition of killing by amphetamine reported previously. However, d-amphetamine but not PEA showed physiologic tolerance following 8 days of twice daily administration. Cross tolerance between the two drugs only occurred when d-amphetamine was administered subacutely. It was concluded that PEA and d-amphetamine have sililar acute effects but differed when given subacutely since PEA did not show tolerance and there was not bidirectional cross-tolerance. These data suggest that these drugs have different pharmacologic actions when given repeatedly. One possible difference may be the duration of action.

Aggression↗
PubMed1978

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats.

The effects of para-chlorophenylalanine (PCPA) on mouse killing behavior were examined in natural killer rats. Forty-eight hr after injection, this serotonin synthesis inhibitor, at relatively low doses of 75 and 150 mg/kg, facilitated mouse killing, as indicated by a decrease in latency to attack the mouse. This effect was revealed in a test of satiation, in which five successive mice were presented to the rat, and also in a novel cage situation. Other than the shorter latencies to attack and kill mice, the killing response was similar in topography to the natural kill. The increase in killing after PCPA injection was associated with a reliable reduction in brain serotonin and in 5-hydroxyindoleacetic acid, and the time courses of the behavioral and biochemical changes were generally similar. In contrast to PCPA, injection of the serotonin precursor 5-hydroxytryptophan (5-HTP, 100 mg/kg) reliably lengthened attack and kill latencies in killer rats. In rats pretreated with PCPA, 5-HTP not only reversed this drug's facilitation of killing, but completely blocked killing in 67% of the rats tested. These results strengthen the hypothesis that brain serotonergic neurons are involved in the inhibition of mouse killing.

5-Hydroxytryptophan↗