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Biomedical subjects

M H Teicher

Publications and source records attributed to M H Teicher.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1988

Increased activity and phase delay in circadian motility rhythms in geriatric depression. Preliminary observations.

Locomotor activity levels and rhythms of eight hospitalized geriatric unipolar depressed patients (DSM-III criteria) were compared with those of eight healthy elderly controls in a similar environment. Activity was measured using a wrist-worn electronic activity monitor with solid-state memory. Depressed patients had a 29% higher mean total 24-hour activity level, with no change in circadian amplitude or frequency. Daily peak activity (acrophase) averaged 2.05 hours later in depressed patients, with no overlap between the groups. The degree of phase delay correlated significantly with the 4 PM postdexamethasone serum cortisol level. These tentative findings suggest that elderly unipolar depressed patients have prominent chronobiological disturbances in the modulation of activity levels and possibly other physiological processes. These differ strikingly from reported disturbances in younger or bipolar depressed patients.

Adult↗
PubMed1988

Decreasing sensitivity to neuroleptic agents in developing rats; evidence for a pharmacodynamic factor.

Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug-receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3-6x) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3-4x) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential "pharmacokinetic" influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO greater than IP greater than ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents.

Administration, Oral↗
PubMed1988

Receptor affinity, neurochemistry and behavioral characteristics of the enantiomers of thioridazine: evidence for different stereoselectivities at D1 and D2 receptors in rat brain.

The binding characteristics of the enantiomers of thioridazine were assessed in the brain of the rat using competitive radioreceptor assays with tritiated ligands selective for dopamine D1 (SCH-23390), D2 (spiperone), norepinephrine alpha-1 (prazosin) and muscarinic (quinuclinidinyl benzilate) receptors. (+)-Thioridazine was shown to have 2.7 and 4.5 times higher affinity than (-)-thioridazine for D2 and alpha-1 receptors, respectively. In contrast, (-)-thioridazine had 10 times higher affinity for the D1 receptor. Both enantiomers showed similar affinities for the muscarinic receptor. In a second experiment, thioridazine, dopamine, norepinephrine, serotonin and their metabolites were assayed in the brain of the rat after acute administration of the enantiomers of thioridazine and the assessment of catalepsy. (+)-Thioridazine was 4.1 times as potent as (-)-thioridazine in elevating the turnover of dopamine in the striatum, but neither enantiomer affected the other monoamines. The concentration of thioridazine and its metabolites in the brain, for a given dose, was similar for both enantiomers. (-)-Thioridazine induced slightly more catalepsy than (+)-thioridazine and appeared to be more toxic at large doses. While racemic thioridazine had an intermediate effect between that of its two enantiomers in the binding and neurochemical assays, it appeared to induce more catalepsy than either enantiomer, suggesting a synergistic effect in this behavioral assay. It was concluded that (+)- and (-)-thioridazine act as partially selective D2 and D1 antagonists, respectively. Therefore, clinical administration of only one enantiomer of thioridazine, rather than the currently prescribed racemate, may result in an improved therapeutic profile and so be worthy of further investigation.

Animals↗
PubMed1988

Amphetamine accelerates and attenuates ultradian activity rhythms in preweanling rats.

Developing rats, studied in environmental isolation, display prominent fluctuations in locomotor activity with a periodicity of about 1-3 hr. This ultradian rhythmic pattern is most marked at 2 weeks of age, and appears to be endogenously mediated. (+)Amphetamine (1 mg/kg) was administered to 2 week old rat pups, and their locomotor activity levels were recorded continuously and stored in 5 min intervals using a sensitive computer-interfaced vibrational activity monitor. Activity was recorded for 12 hr after treatment and resulting time-series data were analyzed by harmonic spectral techniques. During the first 6 hr of testing, amphetamine induced a prominent low frequency perturbation in baseline activity levels corresponding to the expected period of acute drug action. During this time, normally prominent ultradian activity rhythms in the range of 8-12 cycles per day (cpd) were diminished in amplitude, even following low frequency smoothing to remove the changes in baseline. Correspondingly, there was also an increase in ultradian rhythm amplitude in amphetamine-treated pups at higher frequencies (32-40 cpd). During the final 6 hr of testing there was a marked suppression of typical ultradian rhythms in amphetamine-treated pups but not in controls. These results suggest that amphetamine treatment both accelerates and attenuates ultradian activity rhythms in developing rats during the acute period of drug action, and produces a prominent diminution in these rhythms during subsequent rebound and recovery periods.

Activity Cycles↗
PubMed1988

Biology of anxiety.

Our understanding of the biological basis of anxiety is far from complete, although our knowledge of both the neuropharmacologic and molecular basis of anxiety has increased. This article reviews our current knowledge of the possible biological basis of generalized anxiety disorder and panic disorder.

Agoraphobia↗
PubMed1988

Severe daytime somnolence in patients treated with an MAOI.

Eight patients with hypersomnolent, anergic major depression benefited markedly from treatment with relatively high doses of phenelzine or tranylcypromine but experienced intense afternoon somnolence and disrupted sleep. Reducing the dose of monoamine oxidase inhibitor (MAOI) or substituting isocarboxazid sometimes provided relief, but altering the schedule of drugs or meals did not. Bedtime sedation alleviated the disrupted sleep but had little effect on daytime somnolence. The mechanism underlying this side effect is unknown; sleep deprivation, narcolepsy, or hypotension does not account for it. Patients given an MAOI should be assessed for this disturbance and cautioned to avoid risk of injury when it occurs.

Adult↗