Role of maternal biochemistry in fetal brain development: effect of maternal thyroidectomy on behaviour and biogenic amine metabolism in rat progeny.

Few studies have addressed the role of biochemicals of maternal origin on fetal neurodevelopment and behavioural outcome. Thyroid deficiency in the thyroidectomized pregnant rat provides an excellent model to study fetal effects of maternal chemistry, as this condition is known to be associated with deficits in motor and cognitive behaviour in human offspring. Based on evidence that thyroid hormone of maternal origin may be an important determinant in regulating these behaviours, we assessed neurobehaviours and regional brain biogenic amine levels in offspring of rats thyroidectomized (Tx) prior to conception.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Persistent Tardive Dyskinesia and Other Neuroleptic-Related Dyskinesias in Tourette's Disorder.

ABSTRACT Two new cases are reported of persistent tardive dyskinesia associated with neuroleptic treatment of patients with Tourette's disorder. Previously, 44 cases were described in 8 published reports, including 36 children and adolescents, but diagnostic criteria were infrequently specified. In our review of these cases, using the criteria of Schooler and Kane but modified by Gualtieri's more conservative duration criteria of 16 weeks, only 2 of these cases were consistent with a diagnosis of persistent tardive dyskinesia.

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.

A mechanism underlying neuroleptic induced oral dyskinesias in rats.

Previously we have found that spontaneous repetitive jaw movements (RJM) in rats can be augmented by dopamine D1 receptor stimulation and attenuated by D2 stimulation or by D1 blockade. We now report that high and low RJM responders can be inbred and that RJM responses in such rats are further augmented during washout from eight months of treatment with fluphenazine, a time when N-propyl-apomorphine induced stereotypy is severely depressed. Moreover, selective D1 receptor inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) fails to reduce RJM.

Site-directed mutagenesis of tyrosine hydroxylase. Role of serine 40 in catalysis.

We have investigated the role of serine 40 (Ser-40) in tyrosine hydroxylase (TH) catalysis of basal and activated enzymes by protein kinase A (PKA)-mediated phosphorylation. Wild type and mutant TH were transiently and stably expressed in AtT-20 cells, and the enzymatic activities of the recombinant enzymes were analyzed. The specific enzymatic activity of transiently expressed TH mutants Ser-40-->leucine or-->tyrosine (Leu-40m or Tyr-40m) was higher than that of the wild type enzyme or of other mutants in which Ser-8, -19, and -31 were replaced by leucine.

Tonic inhibition of striatal dopamine transmission: effects of benzodiazepine and GABAA receptor antagonists on extracellular dopamine levels.

At present, it is unclear whether ligands which bind at the benzodiazepine/GABA receptor complex play a tonic modulatory role with regard to striatal dopamine (DA) transmission. The present study was designed to examine the effects of Ro15-1788, a benzodiazepine (BZ) receptor antagonist, and SR 95531, a GABAA receptor antagonist, on striatal extracellular DA (DA[e]) concentrations in anesthetized and awake rats using the technique of in vivo microdialysis. Local administration of Ro15-1788 resulted in a dose-dependent increase in DA[e] in both anesthetized and awake animals.

Receptor reserve for D2 dopaminergic inhibition of prolactin release in vivo and in vitro.

The full dopamine agonist R-(-)-N-n-propylnorapomorphine (NPA) completely suppressed (ED50 0.12 micrograms/kg) serum prolactin (PRL) levels elevated by pretreatment with gamma-butyrolactone (750 mg/kg). Pretreatment with the receptor-inactivating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1 and 2 x 6 mg/kg) progressively shifted the dose-response curve for NPA to the right, but PRL secretion was still maximally inhibited.