Aggressive behavior and Brunner syndrome: no evidence for the C936T mutation in a population sample.
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Aggression↗
Biomedical subjects
F R Ervin
Publications and source records attributed to F R Ervin.
Ibogaine in the treatment of heroin withdrawal.
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Animals↗
An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys.
An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine and tyrosine (the amino acid precursors of catecholamine neurotransmitters), would influence dopamine and noradrenaline metabolism. Five hours after the administration of this mixture to vervet monkeys, cerebrospinal fluid levels of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol were reduced by 27.4% and 26.9%, respectively. Both effects were statistically significant. Plasma tyrosine (-30%) and the ratio of tyrosine to the sum of other large neutral amino acids (sigmaLNAA) were also significantly reduced. The behavioral efficacy of phenylalanine/tyrosine depletion was compared with that of tryptophan depletion in a primate model of voluntary alcohol consumption. All three drinks lowered alcohol consumption, but the effects of the tryptophan-deficient amino acid mixture were not different from those of the balanced amino acid control. The phenylalanine/tyrosine-deficient drink differentially lowered alcohol consumption, consistent with other data in this species and elsewhere implicating dopamine in the rewarding effects of alcohol.
Alcohol Drinking↗
Altered dopamine transporter densities in alcohol-preferring vervet monkeys.
Altered dopamine (DA) transporter densities have been implicated in mechanisms of vulnerability and relapse in human alcoholics. The regional distribution and density of the DA transporter was studied in alcohol-preferring vervet monkeys to investigate baseline status and regulation of the DA transporter at different stages of chronic alcohol drinking. Combined ligand binding and in vitro autoradiography of the cocaine congener [125I]RTI-55 (beta-CIT) demonstrated a significant increase in DA transporter densities in abstinent alcohol-preferring monkeys over those in alcohol-avoiding monkeys. Chronic alcohol consumption down-regulated DA transporter densities, and this effect was reversed by acute withdrawal. These results demonstrate that the DA transporter is regulated by alcohol exposure and suggest that increased DA transporter densities may be a phenotypic marker of alcohol preference in vulnerable monkeys.
Alcohol Drinking↗
Strategic business planning for internal medicine.
The internal medicine generalist is at market risk with expansion of managed care. The cottage industry of Academic Departments of internal medicine should apply more business tools to the internal medicine business problem. A strength, weakness, opportunity, threat (SWOT) analysis demonstrates high vulnerability to the internal medicine generalist initiative. Recommitment to the professional values of internal medicine and enhanced focus on the master clinician as the competitive core competency of internal medicine will be necessary to retain image and market share.
Economic Competition↗
Acute effect of altered tryptophan levels and alcohol on aggression in normal human males.
Normal males received amino acid mixtures designed to raise or lower tryptophan availability, and thus to raise or lower brain serotonin synthesis. They also received alcoholic or non-alcoholic drinks. The subjects were tested in the Taylor Competitive Reaction Time Task in which they competed against a (non-existent) partner in a reaction time task. The magnitude of electric shocks that the subjects were willing to give to their bogus partner was used as a measure of aggression. Lowered tryptophan levels and ingestion of alcohol were associated with increased aggression. Our data support the idea that low serotonin levels may be involved in the etiology of aggression. They suggest that subjects with low brain serotonin levels may be particularly susceptible to alcohol-induced violence.
Adolescent↗
A contribution to the differential diagnosis of the "group of schizophrenias": structural abnormality of chromosome 4.
A structural abnormality of chromosome 4 [inv 4 (p15.2; q21.3)] is reported in a male presenting with DSM-III-R schizophrenia, undifferentiated type (295.94) and in his mother, who displayed symptoms associated with schizotypal personality disorder (DSM-III-R 301.22). The proband had a performance IQ of 91, poor motor coordination, stature in the lowest quartile and an impaired sense of time. There were no diagnostic physical or neurological abnormalities. Mild ventricular enlargement and prominent sulci were found on computed tomography. Both he and his chromosomally normal father had strabismus which required surgical correction. This case joins the long list of chromosomal abnormalities previously reported to confer an increased risk of mental illness and emphasizes the importance of a sophisticated differential diagnosis in evaluating patients who present with symptoms of schizophrenia. The implications for recent initiatives which attempt to localize genes conferring susceptibility to schizophrenia and other major mental illnesses are discussed.
Chromosome Aberrations↗
Rationalizing decisions for diagnostic testing.
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Diagnostic Tests, Routine↗
Voluntary alcohol consumption in vervet monkeys: individual, sex, and age differences.
The patterns of voluntary alcohol consumption were studied in 35 vervet monkeys (Cercopithecus aethiops), classified into four groups. Each monkey showed a fairly steady rate during the studied period, resulting in individual differences that became more evident as the treatment evolved. Females showed higher alcohol intake frequencies than males. This sexual difference was maintained among adults and juveniles. Age differences were also observed: juveniles showed higher frequencies of intake than adults, both in general and in each sex group. Intake frequency was not related to age in prepubertal subjects, neither in general nor in each particular sex. The origin of these sex and age alcohol consumption differences remains to be studied, but differences in alcohol metabolism and factors related to puberty are possible influences.
Aging↗
Primate nucleus basalis of Meynert p75NGFR-containing cholinergic neurons are protected from retrograde degeneration by the ganglioside GM1.
The effects of unilateral devascularizing lesions of the neocortex in primates (Cercopithecus aethiops) on the immunoreactivity of choline acetyltransferase and the low-affinity nerve growth factor receptor (p75NGFR) were investigated in cell bodies of the nucleus basalis of Meynert. Choline acetyltransferase enzymatic activity was measured in the dissected ipsi- and contralateral nucleus basalis of Meynert as well as in the remaining cortex adjacent to the lesion. Cortically lesioned animals displayed a shrinkage of p75NGFR-immunoreactive cholinergic cell bodies in only the intermediate portion of the nucleus basalis of Meynert as well as a depletion of choline acetyltransferase activity in this cellular complex. In contrast, cortically lesioned monkeys treated with monosialoganglioside did not reveal a significant loss of choline acetyltransferase activity or shrinkage of nucleus basalis of Meynert cholinergic neurons, but rather a modest hypertrophy. These results are discussed in relation to a possible use of putative trophic agents in the repair of the damaged central nervous system.
Animals↗
Long-term protective effects of human recombinant nerve growth factor and monosialoganglioside GM1 treatment on primate nucleus basalis cholinergic neurons after neocortical infarction.
Neocortical infarction induces biochemical and morphological retrograde degenerative changes in cholinergic neurons of the rat nucleus basalis magnocellularis [Sofroniew et al. (1983) Brain Res. 289, 370-374]. In the present study, this lesion model has been reproduced in the non-human primate (Cercopithecus aethiops) to investigate whether degenerative changes affecting the cortex surrounding the lesioned area and the ipsilateral basal forebrain are prevented by the early administration of recombinant human nerve growth factor alone or in combination with the monosialoganglioside GM1. Six months after surgery and treatment, the monkeys were processed either for biochemistry (choline acetyltransferase assay) or immunocytochemistry. In lesioned vehicle-treated animals, choline acetyltransferase activity significantly decreased by 28% in the cortex surrounding the injured area and by 31% in the ipsilateral nucleus basalis of Meynert when compared with values of sham-operated monkeys. These biochemical changes were fully prevented with the administration of nerve growth factor alone or in combination with the monosialoganglioside GM1. The morphometrical analysis revealed a significant shrinkage of cholinergic neurons (61 +/- 1.4% of sham-operated cell size) and loss of neuritic processes (59 +/- 10% of sham-operated values) within the intermediate nucleus basalis region of lesioned vehicle-treated animals. Although a protection of the cholinergic cell bodies within the nucleus basalis was found with both treatments, a significant recovery of the neuritic processes (84 +/- 7.2% of sham-operated values) was assessed only in the double-treated monkeys. These results indicate that the early administration of nerve growth factor alone or in combination with the monosialoganglioside GM1 induces a long-term protective effect on the nucleus basalis cholinergic neurons in cortical injured non-human primates.
Animals↗
Effect of sucrose consumption on alcohol-induced impairment in male social drinkers.
Two studies were conducted to examine the interaction between sucrose and ethanol in normal young fasting adult males. The first experiment employed a 3 (100 g sugar, 35 g sugar, 0 g sugar) x 3 (alcohol, placebo and sober) factorial design, which was carried out double-blind using aspartame to ensure that all the drinks were equally sweet. Subjects were tested for mood, memory, subjective intoxication and psychomotor performance at baseline and at times up to 3.5 h after ingestion of the drinks. An alcohol by sugar interaction was seen at 0.5 after drinking. Sugar attenuated alcohol intoxication at this time without influencing blood alcohol levels. Contrary to previous reports, the combination of alcohol and sugar failed to produce significant hypoglycemia, or any of the adverse behavioral effects associated with hypoglycemia, at later times after drink ingestion. The second experiment involved a simpler design, carried out single-blind in which the subjects receiving no sugar did not get aspartame. This was to rule out the possibility that aspartame was exacerbating alcohol intoxication instead of sugar attenuating it. The second experiment also showed that sugar can attenuate alcohol intoxication in fasting humans without altering blood alcohol levels significantly.
Adult↗
Voluntary consumption of beverage alcohol by vervet monkeys: population screening, descriptive behavior and biochemical measures.
Seventeen percent of 196 feral vervet monkeys (Cercopithecus aethiops) spontaneously drank appreciable quantities of beverage alcohol in 3% sucrose in preference to 3% sucrose alone. Ethanol consumption increased over time, as did the concentration of ethanol tolerated. Willingness to select ethanol was stable over a three-year period, as measured by periodic retesting. Individual patterns of drinking and behavioral responses to ethanol were quite variable. Upon occasion, some animals drank to ataxia and unconsciousness; signs of withdrawal, including tremulousness, pacing, irritability and increased aggression, followed the abrupt discontinuation of ethanol availability. A variety of changes in social interaction, including increased orientation to external stimulus, increased incidence of stereotyped aggression and of other stereotyped behaviors and decreased frequency of affiliative behaviors were observed during ethanol periods, as compared to baseline scoring periods. In a small number of alcohol-preferring animals, CSF amine metabolites (5-hydroxyindoleacetic acid and homovanillic acid) were raised by drinking alcohol. These studies suggest that the alcohol-selecting vervet monkey may be complementary to established primate models of alcoholism.
Alcohol Drinking↗
Characterization of a primate model of hypertension. The response of hypertensive and normotensive male vervets (Cercopithecus aethiops) to cold pressor stress, captopril administration, and acute bolus of atrial natriuretic factor.
In feral populations of African green monkeys or vervets (Cercopithecus aethiops), between 5 and 15% of adults have spontaneously elevated blood pressure (BP). We report here the initial biological and pharmacological characterization of this potential animal model of hypertension. Captive male monkeys with elevated systolic pressures show a modest pressure increase in response to stressors such as capture, phlebotomy and cold challenge. Acute captopril administration lowers BP in monkeys with high blood pressure (HBP), but has no effect on BP in control animals. Furosemide does not acutely reduce BP. Animals with elevated BPs have lower levels of angiotensin II than do age- and weight-matched controls. An acute infusion of atrial natriuretic factor (ANF) diminishes BP and stimulates urinary output in control and HBP vervets. However, both effects are more pronounced in animals with HBP. Heart rate is not affected by any of the experimental manipulations. Taken together, these data suggest that African green monkeys with spontaneously elevated BP may be a useful experimental model for particular types of human hypertension. Additional studies are required to complete the endocrine and pharmacological characterization of individual animals with HBP.
Analysis of Variance↗
Hypoxanthine accumulation and dopamine depletion in Lesch-Nyhan disease.
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Adenosine↗
Biochemical aspects of tryptophan depletion in primates.
We studied the degree of plasma tryptophan depletion produced by giving normal human males different amounts of a tryptophan-free (T-) amino acid mixture. From the results of this and other studies we concluded that the maximum degree of tryptophan depletion can be produced by a 31.5 g mixture of seven essential amino acids. Administration of a T- amino acid mixture to vervet monkeys lowered tryptophan and 5-hydroxyindoleacetic acid in the cerebrospinal fluid. Levels of tyrosine and the catecholamine metabolites were unchanged. These data support the idea that the effects of T- mixture on mental function in humans which have been reported previously are due to a decrease in 5-hydroxytryptamine.
Adolescent↗
Adenosine analogs inhibit fighting in isolated male mice.
The potent adenosine analogs N-ethylcarboxamide adenosine (NECA) and phenylisopropyladenosine (PIA) inhibit fighting and associated agonistic behaviors in isolated male mice. These effects are reversed by methylxanthines; moderate doses of NECA which inhibit fighting have minimal effects on spontaneous locomotor activity. At very low doses, both NECA and PIA increase fighting in parallel with previously reported increases of motor activity. Brain levels of [3H]-NECA and [3H]-PIA achieved at behaviorally effective doses suggest an involvement of adenosine receptors. The biochemical mechanism of adenosine receptor action with respect to fighting is unknown, but may include neuromodulatory effects on the release of other, more classical neurotransmitters.
Adenosine↗
The effect of breakfast on social behavior and brain amine metabolism in vervet monkeys.
Two groups of vervet monkeys were fed, on alternate days, either before or after a morning observation period. This enabled us to determine changes in behavior when the animals were fed a nutritionally balanced breakfast of monkey chow. Feeding did not alter the proportion of behaviors that were social or non-social, but had a marked effect on individual behaviors. Feeding increased active behaviors among the adult animals except for the vervets who were lowest in the social hierarchy in each cage. For some of the individual behaviors that were altered by feeding, the changes were most marked early on in the observation period, when the animals were still feeding. Other behavioral changes were seen only later in the observation period, a time course consistent with a food-mediated change in brain biochemistry. A parallel biochemical experiment showed that feeding decreased the levels of tryptophan and 5-hydroxyindoleacetic acid in the CSF. Our data indicate that feeding can influence both brain biochemistry and behavior. The behavioral changes may be influenced by social and psychological factors as well as changes in brain biochemistry.
Aging↗