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Biomedical subjects

A J Friedhoff

Publications and source records attributed to A J Friedhoff.

At least 19 recordsLinked to original sources
PubMed2000

Cognitive factors and stress-induced changes in catecholamine biochemistry.

The purpose of the present research was to determine whether dysfunctional attitudes, a cognitive attribute, predicted changes in catecholamine biochemistry. A cognitive task was used to induce stress in female subjects (n=21), and levels of plasma norepinephrine (NE) and homovanillic acid (HVA) were measured at three time points: at baseline (T1); immediately after stress exposure (T2); and 40 min later (T3). Dysfunctional attitudes were significantly and positively related to levels of plasma NE at T3, controlling for baseline levels. Dysfunctional attitudes were not significantly related to plasma HVA levels at any time point. Our findings provide initial support for the idea that dysfunctional attitudes, an attribute shown to play an important role in some forms of unipolar depression, predict stress-induced alterations in noradrenergic output.

Adult↗
PubMed2000

Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.

OBJECTIVE: This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults. METHOD: A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50-150 mg/day) or nortriptyline (25-100 mg/day). RESULTS: The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment. CONCLUSIONS: Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.

Age Factors↗
PubMed1999

Effects of repeated amphetamine treatment on regional GABAA receptor binding.

The present study examined the effects of repeated exposure to amphetamine on GABAA receptor binding in cortical and subcortical areas. The goal of the study was to determine whether changes in specific binding were related to behavioral sensitization. Animals were exposed to either saline (0.3 ml, s.c.; n=12) or d-amphetamine (2.5 mg/kg, s.c.; n=12) for 6 consecutive days and sacrificed after a 14-day withdrawal period. Differences in GABAA receptor binding in these two groups of animals were assessed using the GABAA receptor antagonist [3H]SR 95531. To verify that the preceding treatment regimen led to the development of behavioral sensitization, a separate set of animals (n=8/group) was exposed to the same regimen and challenged with d-amphetamine (2.5 mg/kg, s.c.) after the 14-day withdrawal period. As expected, preexposure to amphetamine led to the development of amphetamine sensitization. There were no differences in GABAA receptor binding in animals preexposed to saline and amphetamine in the prefrontal cortex, caudate-putamen, hypothalamus, or cerebellum. These findings do not provide support for the idea that changes in GABAA receptor binding in the medial prefrontal cortex or various subcortical areas are related to the development of behavioral sensitization.

Adrenergic Agents↗
PubMed1999

The effect of novel antipsychotics in rat oral dyskinesia.

1. The effect of the D1 agonist SKF38393 and the 5HT2C agonist m-CPP on repetitive jaw movements (RJM) was studied in rats. Acute administration of SKF38393 and/or m-CPP induced RJM in a dose dependent manner. In rats treated with both drugs, RJM responses were about equal to the sum of those obtained with each drug alone. 2. The induction of RJM by SKF38393 was somewhat lower in rats pretreated with 5HT2C receptor antagonist, mianserin, whereas mianserin severely reduced RJM induced by m-CPP alone. 3. D1 antagonist SCH23390 inhibited SKF38393 induced RJM but had no effect on m-CPP induced chewing behavior. 4. The present study confirms earlier evidence that D1 agonists used at optimal doses for the induction of RJM do not involve the serotonergic system in a significant way. It does, however, implicate the system in the emergence of drug induced oral behavior in rats. 5. The effect of the atypical antipsychotics, clozapine, olanzapine and risperidone was studied on SKF38393 and m-CPP induced RJM. Pretreatment with the atypical antipsychotics clozapine and olanzapine inhibit SKF38393 and m-CPP induced RJM. Pretreatment with risperidone inhibits m-CPP induced oral behavior in rats while increases dose dependently SKF38393 induced RJM.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

A phosphoinositide-linked dopamine D1 receptor mediates repetitive jaw movements in rats.

BACKGROUND: We have demonstrated that rats injected with D1 agonists SKF 38393 or A68930 demonstrate repetitive jaw movements (RJM). These agonist-induced movements in rats are similar in their appearance to those induced in rats by long-term treatment with antipsychotic drugs. Over recent years D-1 receptors were discovered which showed linkage not only to c-AMP but also to PI hydrolysis. We examined the effect of EEDQ inactivation of D1 receptors on D-1 mediated PI hydrolysis and RJM. METHODS: Twenty four hours following EEDQ or vehicle administration D-1 agonists or vehicle were administered. The number of RJM episodes was assessed in EEDQ and vehicle treated rats. D-1 receptor density and inositol phosphate formation were determined in the striata. RESULTS: EEDQ administration resulted, 24 hours later, in 70-80% selective depletion of D-1 receptors in the striata but did not modify the rate of RJM induced by D-1 agonists. There was no significant difference in D-1 mediated PI hydrolysis in EEDQ treated rats when compared to vehicle treated group. CONCLUSIONS: The present data support the earlier demonstration of D-1 agonist induced RJM, an effect mediated by a subpopulation of a D-1 receptor subtype and constitute the first behavioral evidence for the existence of a behavioral response mediated by D-1 like dopamine receptors linked to an alternate second messenger system-PI hydrolysis.

Animals↗
PubMed1997

Differential regulation of D2 receptor gene expression by transcription factor AP-1 in cultured cells.

The role of the transcription factor AP-1 in regulating D2 receptor transcriptional activity was investigated in D2 receptor expressing neuroblastoma cells, NB41A3, and in non-D2 receptor expressing CHO cells. Deletion of a region containing the putative AP-1 binding site resulted in a significant reduction in the activity in CHO cells; while the activity in NB41A3 cells was increased suggesting that the AP-1 site may differentially regulate D2 gene expression in these distinct cell types. However, both cell lines were found to express significant and similar levels of the transcription factors AP-1. Analysis of phosphorylated proteins in each of the cell lines provided evidence that AP-1 is phosphorylated in NB41A3 cells, but not in CHO cells. This result suggests that differential regulation of D2 gene expression may be related to AP-1 phosphorylation.

Animals↗
PubMed1997

Vulnerability to stress: self-criticism and stress-induced changes in biochemistry.

It has been hypothesized that individuals who are high on the attribute of self-criticism are particularly vulnerable to failure stress. To test this hypothesis, we examined the relationship between self-criticism and changes in plasma homovanillic acid (HVA; the metabolite of dopamine) and emotion during exposure to an induced-failure task. Participants consisted of 21 women. Plasma HVA and emotion were assessed at three time points: baseline (T1), during stress exposure (T2), and 40 minutes after cessation of the stressor (T3). We found that self-criticism was significantly and positively related to changes in plasma HVA during stress exposure. In addition, the personality attribute was significantly and positively related to subjective ratings of stress and changes in scores on the Confusion-Bewilderment scale of the Profile of Mood States during the task. To our knowledge, this is the first study to report that self-criticism is related to stress-induced changes in biochemistry.

Adult↗
PubMed1996

Novelty-associated locomotion: correlation with cortical and sub-cortical GABAA receptor binding.

The present study was designed to determine whether variability in GABA (eta-aminobutyric acid)A receptor binding in cortical and subcortical brain regions was correlated with locomotor activity in a novel environment. Twenty four animals were rated for locomotor activity in a novel circular runway. Eight days later, locomotor activity was assessed following 1.5 mg/kg amphetamine sulfate (i.p.). After four to six days, animals were killed and samples were pooled in groups of four animals ranked according to novely locomotor score, and specific binding of the GABAA receptor antagonist [2-(3'-carboxy-2'-propyl)-3-amino-6-p-methoxy phenylpyridazinium bromide] ([3H]SR95531) was determined. Significant negative correlations were seen between specific ([3H]SR95531) binding and novelty induced locomotion in the cingulate and prefrontal cortices, and in the ventral pallidum. A near-significant negative correlation was seen in the striatum. Correlation coefficients between locomotion scores in the novel environment and specific [3H]SR95531 binding were: cingulate cortex, R = -0.91, P = 0.012; prefrontal cortex, R = -0.85, P = 0.032; ventral pallidum, R = -0.85, P = 0.030; striatum, R = -0.73, P = 0.097; and nucleus accumbens, R = -0.09, P = 0.85. The positive correlation between novelty- and amphetamine-induced locomotion was also quite high (R = 0.95, P = 0.004). These results are discussed in terms of their relevance to potential biochemical correlates of drug abuse vulnerability.

Animals↗
PubMed1996

Causes of haloperidol discontinuation in patients with Tourette's disorder: management and alternatives.

BACKGROUND: Neuroleptics are considered the mainstay of treatment in Tourette's disorder, and haloperidol is deemed the treatment of choice by many. Factors such as treatment efficacy and the side effects that appear in response to neuroleptic administration have been implicated in affecting medication compliance. However, a detailed evaluation of these factors has yet to be undertaken in Tourette's disorder. METHOD: Of 51 consecutive referrals to a Tourette's disorder clinic, 48 met DSM-III-R criteria for Tourette's disorder. Of these 48, 28 had previously received neuroleptics. In this set of 28 patients, 24 (16 male, 8 female) had initially received treatment with haloperidol, and they made up the present sample; their ages ranged from 10.4 to 47.9 years (mean = 27.1), and age at onset ranged from 2 to 16 years. Each patient completed an evaluation consisting of a Tourette Syndrome Questionnaire and a clinical interview with the patient and involoved family members. Charts were also reviewed to gather information concerning side effects and other factors that led to haloperidol discontinuation and/or noncompliance. RESULTS: Duration of treatment ranged from 3 days to 14 years (mean = 3.6 years). In this sample, 12.5% (3/24) of the subjects continued medication without interruption (mean +/- SD = 8.4 +/- 5.1 years of medication). Of the 21 patients who discontinued haloperidol, 66.7% (14/21) did so because they experienced intolerable side effects, 9.5% (2/21) because of the fear of experiencing certain side effects, and 14.3% (3/21) because of a combination of these factors. The principal side effects that led to discontinuation included dysphoric reactions, akathisia, nervousness, sedation, dystonic reactions, and cognitive dulling/feeling drugged. CONCLUSION: Careful monitoring of side effects and efficacy is essential to continued compliance with haloperidol. In addition, psychoeducation about potential consequences of medication administration may help promote compliance in those patients who develop fears of possible adverse reactions.

Adolescent↗
PubMed1995

Alterations in GABAA receptor binding in the prefrontal cortex following exposure to chronic stress.

The present study was designed to examine the effects of chronic stress on GABAA receptor binding. Animals were randomly assigned to either a control, acute, or chronic stress condition and changes in specific binding were assessed using the GABAA receptor antagonist [3H]SR 95531. Exposure to chronic restraint stress led to a significant reduction in GABAA receptor binding in the prefrontal cortex. Alterations in specific binding were not observed in the cerebellum, caudate-putamen, hippocampus, or cingulate cortex however, suggesting that the effects of chronic stress may be regionally specific. Exposure to acute restraint did not lead to a significant alteration in [3H]SR 95531 binding in any brain region examined.

Animals↗
PubMed1995

Schizophrenia: gender, family risk, and plasma homovanillic acid.

Plasma homovanillic acid concentration was assessed in 60 young schizophrenic patients, with and without first-degree relatives with schizophrenia, before treatment, and 3 days after starting haloperidol treatment. The baseline concentration of homovanillic acid in plasma was no different in the two groups before treatment; it was, however, significantly higher in the patients with relatives than in those without relatives diagnosed of schizophrenia after 3 days of haloperidol treatment.

Adolescent↗
PubMed1995

Repeated inescapable stress produces a neuroleptic-like effect on the conditioned avoidance response.

This study tests the hypothesis that the dopaminergic system mediates a restitutive response by decreasing its own activity in the face of events like persistent inescapable stress that threaten to interrupt organized mental activity. It is well established that neuroleptic drugs inhibit the conditioned avoidance response (CAR), but not the escape response, probably via a reduction in subcortical dopaminergic activity. We trained rats to perform the CAR and then subjected them to acute and chronic stress to determine whether this would result in inhibition of the CAR. Rats subjected to twice daily tailshock stress for 8 days showed inhibition of the CAR and a reduction in dopamine (DA) utilization in the nucleus accumbens. These findings are compatible with the hypothesis that an endogenous DA-dependent mechanism exists that mimics neuroleptic effects in the face of repeated stress. In humans this response may serve as a protection against psychotic decompensation from chronic endogenous or exogenous insult.

Animals↗
PubMed1995

Environmental factors and related fluctuation of symptoms in children and adolescents with Tourette's disorder.

The purpose of this paper is to assess how 29 different environmental factors affected Tourette symptomatology in 14 children and adolescents (6.6-14.5 years; mean 10.3) who had never received any medication for their disorder. Assessment was based on patients' responses to the Tourette Syndrome (TS) Questionnaire. Eleven different factors were associated with a decrease in symptoms and included doctor visits, talking to friends, and reading for pleasure. The 10 factors reported to have no impact on Tourette symptomatology included various foods, weather, and living away from home. Seventeen factors associated with an increase in Tourette symptoms included events causing anxiety, emotional trauma, and social gatherings.

Adolescent↗
PubMed1994

Possible genetic factors underlying the pathophysiology of tardive dyskinesia.

Rates of spontaneous and drug-induced repetitive jaw movements (RJM) in rats vary widely. Low and high RJM responders were isolated and genetically selected. At each generation mean RJM responses (spontaneous or SKF 38393-induced) of the two types of rats were found to differ significantly, whereas neither apomorphine-induced stereotypic responses nor D1 and D2 receptor numbers and affinities differed. A significant increase in cAMP production was evident in SKF 38393-stimulated striatal homogenates of high RJM responders as compared with low responders. Animals subjected to 8-months exposure to fluphenazine exhibited RJM that were about twice as great as that of controls, 2 months after the last treatment, with a prevalence of about 75%. Similarities between RJM observed in rats and neuroleptic-induced tardive dyskinesia suggest that the two are strongly related.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

A subpopulation of dopamine D1 receptors mediate repetitive jaw movements in rats.

Repetitive jaw movements (RJM) in rats, a potentially useful animal model of tardive dyskinesia, appears to be mediated by the dopamine D1 receptor as evidenced in part by their induction and inhibition with D1 agonists and D1 antagonists, respectively. Selective destruction of 60-90% of D1 receptors by EEDQ, measured in several CNS dopaminergically innervated areas, preceded by protection of D2, 5-HT2, alpha 1 and alpha 2 receptors, however, failed to reduce D1 agonist-augmentable RJM. Further, the affinity of dopamine toward displacement of 3H-SCH-23390 binding from striatal D1 receptors was significantly decreased by administered EEDQ, a counter-intuitive result in relation to D1 responsitivity and RJM. Thus, at present it is suggested that an EEDQ-resistant D1 receptor subpopulation may exist.

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