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Biomedical subjects

M H Teicher

Publications and source records attributed to M H Teicher.

At least 19 recordsLinked to original sources
PubMed1992

Olfactory bulbectomy as a model for agitated hyposerotonergic depression.

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.

Amitriptyline↗
PubMed1992

Quantitative assessment of psychomotor activity in patients with neuroleptic-induced akathisia.

1. An ambulatory activity monitor with solid-state memory was employed to obtain 24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9 normal controls. 2. The activity monitor is a piezoelectric device which was strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of akathisia and lower levels of daytime activity. 4. Manic and depressed patients showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement of activity may be complicated by the patient's psychiatric disorder.

Adolescent↗
PubMed1991

Dopamine D1 autoreceptor function: possible expression in developing rat prefrontal cortex and striatum.

Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using gamma-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) after inhibition of aromatic L-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D1 agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D1 partial agonist CY-208-243, and were blocked by the D1 antagonist SCH-23390, suggesting receptor mediation. The mixed D2/D3 agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D1-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D2-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Circadian locomotor activity rhythms in Alzheimer's disease.

Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment.

Aged↗
PubMed1990

Dopamine D1 receptor development depends on endogenous dopamine.

Profound depletion of forebrain dopamine by 6-hydroxydopamine in neonatal rats (day 3) was associated with up to 82% loss of D1 receptor sites labeled with [3H]SCH-23390 at day 21. Administration of the selective D1 agonist SKF-38393 (days 6-18) abolished the correlation between D1 receptor density and DA concentrations, even with greater than 99% depletion of DA. In intact control animals, there was an inverse correlation between spontaneous variation in levels of DA and D1 receptor site density in forebrain tissue (r = -0.79) which also was abolished by treatment with the D1 agonist. Thus, D1 receptor density may be regulated by reciprocal regulatory processes during normal development, but may fail to develop in the absence of an adequate level of stimulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Olfactory bulb control of circadian activity rhythm in mice.

Ablation of mouse olfactory bulbs lengthened the circadian period of wheel-running activity by 43 min and delayed the onset of entrained activity by 108 min. A transient increase in activity during the light phase of the 12:12 h light-dark photoperiod also occurred following surgery. These disruptions suggest that olfactory systems can modulate mammalian circadian rhythms.

Animals↗
PubMed1990

COSIFIT: an interactive program for simultaneous multioscillator cosinor analysis of time-series data.

A BASIC program for the Macintosh family of computers has been developed that provides an iterative nonlinear least-squares analysis of biological rhythm data using Marquardt's modification of the Gauss-Newton algorithm. A cosinor model is used, and multiple cosine functions can be fit simultaneously to any equi- or unequispaced time-series data. The program computes optimal frequency, mesor, amplitude, and phase, with standard errors of measurement and both parametric and nonparametric estimates of goodness-of-fit. Multiple time-series can be analyzed simultaneously, allowing one to test for shared characteristics between series. Statistical differences between parameter values of select curves are ascertained by ANOVA. The program is interactive and designed to be user-friendly for the scientist or clinician.

Adult↗
PubMed1990

Emergence of intense suicidal preoccupation during fluoxetine treatment.

Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these patients had ever experienced a similar state during treatment with any other psychotropic drug.

Adult↗
PubMed1990

Seasonal affective disorder: rapid resolution by low-dose alprazolam.

Seasonal affective disorder (SAD) has recently been recognized as a common psychiatric disorder, and treatment with bright artificial light has been shown to be effective in treating fall-winter SAD. However, many patients with SAD fail to respond or find phototherapy too inconvenient. We thus assessed the efficacy of alprazolam in 6 patients diagnosed with SAD during the course of ongoing clinical treatment. Alprazolam was administered in doses ranging from 0.5 mg to 1.5 mg daily. This agent produced rapid and dramatic results in 4 patients, with remission of symptoms occurring in about 3 days. These patients initially became hypomanic or hyperthymic, and then settled into a state of euthymia about 2 weeks later. Two patients had a moderate response but were still symptomatic. Five subjects received continuous treatment for at least an entire season, and none experienced withdrawal symptoms upon discontinuation. Alprazolam may represent an effective and well-tolerated alternative treatment for SAD.

Adolescent↗
PubMed1989

Postnatal development of dopamine D1 and D2 receptor sites in rat striatum.

Tissue was obtained from corpus striatum of maturing rats at representative postnatal ages of 8-120 days for evaluation of D1 and D2 dopamine (DA) receptor sites in radioreceptor assays based on use of 0.05-2.5 nM concentrations of [3H]SCH-23390 or [3H]domperidone, respectively. Pharmacologic selectivity was verified by high rank-correlations (rs greater than 0.90) of Ki values for representative test agents in both assays (vs 0.3 nM ligand), using striatal tissue obtained at ages 20 and 120 days. Data from repeated (3-5x) six-concentration isotherm experiments involving a wide range of D1 or D2 radioligand concentrations were analyzed by linear regression of specific binding (B) vs free ligand concentration (F) in linearized form (B/F vs B) for each replicate assay and for pooled values, as well as by curve-fitting all available raw data (B vs F) using the LIGAND program adapted to microcomputer. Values for apparent ligand affinity (Kd = 0.15-0.35 nM) failed to show a consistent change with age, while values for apparent receptor site density (Bmax) followed a similar developmental course with both methods of analysis (between methods: r = 0.99 and 0.89 for D1 and D2 assays, respectively, across all ages tested).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Effects of selective monoaminergic reuptake blockade on activity rhythms in developing rats.

Developing rats display prominent ultradian rhythms of locomotor activity when separated from the litter. A pharmacological analysis was undertaken to provide preliminary data on the role of monoaminergic neurotransmitter systems in the modulation or manifestation of this fundamental biological rhythm. Twenty-four hour activity profiles were monitored in 15-day-old rats, tested in darkness, after intraperitoneal treatment with desipramine (DMI), zimelidine (ZMI), or GBR-13069 (GBR), selective uptake inhibitors of norepinephrine, serotonin, and dopamine, respectively. Time series data were analyzed by low-resolution variance spectral analysis. DMI significantly diminished ultradian (greater than 1 cycle per day; cpd) rhythmicity, and enhanced the circadian rhythm. Equimolar doses of ZMI had little effect on the ultradian band (7-15 cpd), but slightly reduced the circadian peak. The effects of acute GBR administration were complex, as this agent produced prominent effects on basal activity. In a second study these agents were administered continuously over a 5-day period, using subcutaneously implanted Alzet osmotic minipumps, to avoid the confounding effects of acute administration. Continuously-infused DMI virtually eliminated characteristic ultradian rhythms in the 9-15 cpd bandwidth. ZIM diminished ultradian oscillations only in the 14-15 cpd range, and GBR-12909 had little effect on ultradian rhythms throughout the usually prominent 7-16 cpd domain. All three reuptake inhibitors increased the prominence of slow ultradian rhythms with frequencies of 3-4 cpd. Continuous reuptake blockade had no significant effects on circadian amplitude or phase, as determined by cosinor analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Bromocriptine antagonizes behavioral effects of cocaine in the rat.

Rats given cocaine or bromocriptine under conditions of low basal arousal showed dose-dependent increases of locomotor activity for less than or equal to 1 hours, followed by depression of activity that diminished gradually over the next 2 hours. Arousal was related biphasically to dose (maximum at ca. 5 mg/kg) but depression increased monophasically with the dose of either agent. Both behavioral arousal and depression induced by cocaine were antagonized by bromocriptine, even at doses lacking behavioral effects alone (ID50 = 1.0 and 0.36 mg/kg [1.3 and 0.5 mumol/kg], respectively). Bromocriptine blocked depression of locomotion even when given after the initial stimulation by cocaine. Bromocriptine induced very weak stereotypy, and neither increased nor blocked stereotypy induced by cocaine or apomorphine. Cocaine, at maximally effective doses, did not deplete catecholamines or serotonin in brain regions at times of maximum behavioral arousal or depression, nor did bromocriptine after metabolic turnover of dopamine. Bromocriptine antagonized arousal induced by direct injection of dopamine into the nucleus accumbens. The ability of bromocriptine to block both the behavioral arousal and depression induced by cocaine may reflect activity of bromocriptine as a mixed agonist-antagonist with limited intrinsic agonistic activity at central dopaminergic D2 receptors, perhaps with particular reference to limbic mechanisms.

Animals↗
PubMed1989

Aging, nutrient choice, activity, and behavioral responses to nutrients.

We directly measured nutrient consumption, activity patterns, and behavior in young volunteers and healthy elderly volunteers (N = 86) living in an identical environment. Compared to the young subjects, the elderly adults consumed fewer calories and less carbohydrate and fat, but not less protein, after adjustment for differences in body weight. Males of both ages consumed more protein than females after adjustment for body weight. All subjects snacked predominantly on carbohydrate-rich foods. The elderly subjects, however, consumed significantly fewer snacks than the young. Patterns of mood and activity also differed between age groups: the elderly volunteers were more active and alert than the young, especially early in the day, as measured by activity monitors and self-report questionnaires. We also examined the behavioral effects of high-protein and high-carbohydrate meals on these subjects because of the effects such meals can have on brain serotonin levels. The subjects ingested isocaloric carbohydrate- or protein-rich breakfasts and dinners and then participated in a series of behavioral tasks. Significant interactions between the type of meal consumed (protein versus carbohydrate) and the time at which they were ingested (breakfast versus dinner were observed. A protein meal consumed at breakfast induced more fatigue and sleepiness than an isocaloric carbohydrate meal; this was reversed in the evening when a carbohydrate meal induced more fatigue. Elderly subjects were less sensitive to sleepiness induced by carbohydrate in the evening. Overall, the young and old adults exhibited significant differences in calorie and carbohydrate intakes and also mood and activity, even when they chose their foods from an identical selection of food items and followed the same basic daily routines while living in a controlled study environment.

Adult↗
PubMed1989

Open assessment of the safety and efficacy of thioridazine in the treatment of patients with borderline personality disorder.

A 12-week open study was conducted to assess the possible efficacy and safety of low-dose thioridazine in 11 outpatients (8 women, 3 men) with borderline personality disorder (BPD) diagnosed according to DSM-III-R (American Psychiatric Association 1987) and the Diagnostic Interview for Borderline Patients (DIB; Gunderson et al. 1981) criteria. Mean thioridazine dose averaged 92 mg per day across the duration of this study. At endpoint, there was a significant reduction in Brief Psychiatric Rating Scale (BPRS; Overall & Gorham 1988) scores, and patients appeared to be less symptomatic on the impulse action patterns, affects, and psychosis subscales of the DIB (modified to assess change). Subjects completing the entire study (n = 6) also showed improvement in interpersonal relations. On self-report measures, significant improvement was noted on most Hopkins Symptom Checklist-90 (SCL-90; Derogatis et al. 1973) subscales, particularly in hostility and additional depressive features. Subjects completing the entire study showed significant improvement in paranoid ideation, interpersonal sensitivity, and anxiety. Three patients, however, developed sustained melancholic depressions that necessitated their discontinuation from the study and the initiation of anti-depressant treatment. These three individuals were more schizotypal, schizoid, and paranoid at baseline according to Personality Disorder Examination (PDE; Loranger et al. 1987) structured interviews. Weight gain was not a significant problem, but sedation and erectile dysfunction were. Overall, these findings suggest that thioridazine may exert prominent effects on patients with BPD and that double-blind, placebo-controlled studies are warranted.

Adult↗
PubMed1988

Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses.

The clinical use of antipsychotic agents may be enhanced by considering their dose-effect characteristics. In particular, assessment of immediate and later follow-up treatment of psychotic patients (1) indicates that moderate doses are adequate for most patients, (2) fails to support the utility of unusually high doses, and (3) even suggests the existence of a biphasic relationship of antipsychotic efficacy to dose of neuroleptics and possibly to plasma concentrations of the drugs as well. Trends toward lesser overall clinical benefits of high doses may reflect untoward extrapyramidal or other central nervous system effects leading to behavioral and cognitive symptoms. Thus, moderate doses of neuroleptics appear, on average, to be about as effective as, and probably safer than, the larger doses that have been popular in the United States in recent years.

Acute Disease↗