Biomedical subjects
Publications and source records attributed to R F Anton.
Impaired cognitive function in the presence of psychotic symptoms is often difficult to diagnose and treat. Carbamazepine, in a longitudinally controlled fashion, improved orientation, memory, and psychotic symptoms in a patient with previously diagnosed bipolar illness and multi-infarct dementia.
Two experiments were conducted to investigate the influence of ovariectomy (OVX) on alcohol sensitivity in mice. In the first experiment, OVX, sham-operated, and nonsurgical control C57BL mice were examined for brain alcohol levels associated with alcohol-induced motor incoordination, alcohol-induced loss of righting reflex, and voluntary alcohol consumption. The second experiment employed four strains of mice (C57BL, C3H, DBA, and Swiss Webster) to evaluate the influence of OVX on alcohol-induced spontaneous activity. Taken together, the results indicated that surgical removal of the ovaries in mice does not influence alcohol-induced motor incoordination, loss of righting reflex, or spontaneous activity. Voluntary alcohol consumption, however, was affected by ovariectomy, since mice in the OVX group consumed less alcohol relative to body weight (g/kg) than controls.
Lithium carbonate is used in several psychiatric disorders in the context of alcohol abuse. In a randomized, double-blind, crossover study the single-dose kinetics of lithium were followed after alcohol or placebo. Lithium carbonate capsules were taken by mouth by 10 healthy young men with alcohol on one occasion and with placebo on a separate occasion (at least 7 days apart). Lithium concentrations were determined in serum and urine samples for 24 hours after dosing and served as the basis for kinetic analysis. Acute alcohol had no effect on lithium absorption, elimination, distribution, or clearance. Alcohol did, however, increase the peak serum lithium level in nine of 10 subjects, from a mean of 0.62 mEq/L in the placebo condition to 0.70 mEq/L in the alcohol condition. Our data suggest that alcohol has limited effects on lithium carbonate kinetics. The possibility of elevated serum lithium concentrations when lithium is taken with alcohol is suggested.
Delusions of parasitosis, or a patient's persistent belief that he has cutaneous invasion by parasites despite medical evidence to the contrary, is an uncommon syndrome associated with a wide variety of medical and psychiatric disorders. Its prognosis has been improved considerably by the introduction of pimozide, a potent neuroleptic agent.
It has been shown that adrenal glucocorticoids have a permissive role in some of the actions of alcohol. To determine if an intact adrenal was necessary for the stimulation of locomotor activity, 24 female C3H mice were tested for open field activity with ethanol or saline. Two weeks after adrenalectomy or sham surgery, animals were tested for activity again with ethanol or saline. One week later, alcohol disappearance curves were generated for blood and brain. Adrenalectomy reduced but did not abolish the alcohol-stimulated locomotor activity. In addition, adrenalectomy significantly reduced estimated peak alcohol levels in blood and brain but significantly reduced the disappearance rate for alcohol only in brain. These data suggest that adrenalectomy significantly changes alcohol distribution, with greater impact on brain alcohol levels than on blood levels, and that this may be responsible, at least in part, for the reduction in stimulated locomotor activity.
A focused microwave fixation technique was tested for use in determining basal PGE and thromboxane B2 levels of mouse brain. Focused microwave irradiation (3.5 Kw/0.4 sec) to the head of C3H mice produced basal values of PGE and TXB2 which were five-fold less than those in animals killed by decapitation. Indomethacin (10 mg/kg) pretreatment blocked the decapitation rise in PGE and TXB2 levels and gave values similar to focused microwave irradiation. Indomethacin pretreatment combined with microwave fixation did not reduce PG levels more than microwave treatment alone. When microwave fixation was used, there was no difference in regional (cerebral cortex, whole cerebellum, midbrain, hypothalamus) levels of either PGE or TXB2. However, PGE levels were significantly higher than TXB2 in all regions. After decapitation there was a greater increase in TXB2 than PGE. The cerebellum produced less PGE and TXB2 after decapitation compared to the other regions. Our results confirm the usefulness of the focused microwave irradiation technique for examining in vivo basal prostaglandin levels in mouse brain.
An animal model was used to examine the effect of maternal alcohol administration on behaviors in the offspring which might predispose to alcoholism. Pregnant C3H mice were administered a liquid diet containing 28% ethanol-derived calories (EDC) from Gestation-Day 8 until parturition. Control animals were either pair-fed an isocaloric 0% EDC diet or received standard lab chow and water throughout pregnancy. Offspring were tested for sleep time following a challenge dose of 3.5 or 4.5 g/kg ethanol at 25 or 110 days of age or for consumption of 10% w/v ethanol in a two-bottle choice situation. The results demonstrated that prenatal exposure to alcohol did not affect alcohol-induced sleep time at either testing age or dose and that waking blood alcohol levels were similar across groups. Voluntary alcohol consumption, however, was higher in mice exposed to alcohol in utero during the initial week of testing but intake decreased to near control levels by the third week. Whether other alcohol-related behaviors are altered by prenatal alcohol exposure remains to be examined.
It has been suggested that the antidepressant amoxapine might have neuroleptic properties. Clinically, an increase in serum prolactin occurs during neuroleptic treatment secondary to post-synaptic dopamine blockade. Ten men who met DSM-III criteria for major depression exhibited a significant increase in their serum prolactin over drug-free baseline values during treatment with amoxapine. A comparison group of 12 depressed men treated with desipramine showed no such increase. Combined with that of others, our study suggests that amoxapine might have antipsychotic properties and, therefore, be useful in treating conditions where a combined antidepressant and neuroleptic effect is required.
The prostaglandin system has been implicated in mediating both the acute and chronic pharmacologic effects of alcohol. The effect of blockade of prostaglandin synthesis by indomethacin on genetically based alcohol preference in C57BL/6, C3H/He, and BALB/c mice was examined. Although strain typical alcohol preference patterns were observed, there was no effect of indomethacin on either naive or preestablished alcohol preference and consumption. Genetically transmitted alcohol preference may be a complex system in which prostaglandin synthesis does not play a part.
Psychotic depression is a distinct clinical entity in that its response to tricyclic antidepressants is poor but its response to tricyclic antidepressant-antipsychotics is better. The authors report the favorable outcome of four patients with psychotic depression treated with amoxapine, a derivative of the antipsychotic loxapine. The elevation of serum prolactin during treatment in three patients suggests that postsynaptic dopamine blockade occurs with amoxapine treatment. This might account for the efficacy of amoxapine in psychotic depression.
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The effect of multiple family therapy on client compliance and retention in a high intervention, naltrexone treatment program was examined retrospectively. The population consisted of 65 opiate-dependent individuals consecutively treated with naltrexone and a standard program of counseling and supportive psychotherapy. Twenty-five of these individuals, in addition, received multiple family therapy. The data presented are suggestive of the efficacy of combining multiple family therapy and high intervention in patients being treated with naltrexone. Analysis of the data demonstrated that the group receiving multiple family therapy had a larger continuous time of naltrexone ingestion and remained in the treatment program longer than clients who did not receive multiple family therapy. These effects were independent of race and employment status. The implication of the results for treatment and avenues for future research are discussed.
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The influence of pre-pregnancy alcohol consumption on alcohol self-selection during pregnancy and lactation was examined in C57BL mice. One group of animals was given a two-bottle choice between water and a 10% w/v ethanol solution for three weeks prior to breeding, throughout pregnancy, and during lactation, while a second group was given the alcohol-water choice beginning on the first day of pregnancy. Relative alcohol intake (g ethanol/kg body weight) as well as alcohol "preference" decreased below pre-pregnancy levels during both pregnancy and lactation. That is, voluntary alcohol consumption was attenuated in pregnant and lactating mice, regardless of strain-typical pre-pregnancy high consumption. However, mice given a choice between alcohol and water prior to pregnancy did not decrease their alcohol consumption during pregnancy as much as mice not given the pre-pregnancy alcohol choice. There was no correlation between pre-pregnancy alcohol consumption and subsequent intake. The mechanism underlying decreased voluntary alcohol consumption during pregnancy remains to be elucidated, but it is clear that prior experience with alcohol influences the phenomenon.
A new potentially useful measure for assessing physical dependence in mice chronically exposed to ethanol is described. C3H/He mice continuously exposed to ethanol vapor for four (Experiment 1) or three (Experiment 2) days spent more time engaged in stereotypic climbing behavior than controls. This stereotypic climbing behavior correlated well, both temporally as well as in intensity, with other previously described signs of ethanol withdrawal. All measures of withdrawal behavior (including climbing) peaked at eight hours after withdrawal and returned to control levels by 30-33 hours. The utility of this behavioral assay for assessing physical dependence on ethanol is further discussed with reference to possible underlying neurochemical events.
Cloninger described a classification system for subtyping alcoholics based on personality dimensions of novelty seeking (NS), harm avoidance (HA), and reward dependence (RD). The relationship between these dimensions and childhood hyperactivity was examined. Mild to moderate alcohol-dependent adults (68 male and 34 female) were administered Tarter's HK/MBD Childhood Symptom Checklist, Cloninger's Tridimensional Personality Questionnaire, and the Beck Depression Inventory. Alcoholics with childhood hyperactivity (38% of sample), regardless of gender, exhibited greater NS than did alcoholics without childhood hyperactivity. Female alcoholics scored significantly higher on RD compared to males. Findings suggest that high NS, proposed by Cloninger as a predominantly male feature, is related to childhood hyperactivity, independent of gender.
Previous investigations of the relationship between drinking patterns and cognitive functioning have generally studied severely alcoholic patients, in whom the neurocognitive effects of alcohol consumption can be obscured by other medical or psychosocial factors. In the present study, cognitive functioning was examined after a minimum of 4 days of abstinence in 69 mildly to moderately alcohol-dependent outpatients without comorbid psychiatric, neurologic, or systemic medical illness. Circumscribed decrements in reaction time and verbal memory were associated with higher amounts of alcohol consumption in the 90 days prior to enrollment in the study, and amount of recent consumption was correlated with scores on numerous cognitive tests. In contrast, longer drinking history was not associated with poorer performance on any neuropsychological measures. Thus, in this group of high-functioning, mildly to moderately alcohol-dependent outpatients, mild cognitive deficits were related to the amount of recent, but not lifetime, alcohol consumption.