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S Caldecott-Hazard

Publications and source records attributed to S Caldecott-Hazard.

At least 19 recordsLinked to original sources
PubMed1995

Developmental neurotoxicity to methamphetamines.

1. To investigate the long-term changes caused by amphetamines in the developing brain, we used both an in vivo and in vitro model of chronic fetal exposure to methamphetamine and related drugs. 2. Offspring of rats, treated with either saline, 2 mg/kg twice a day (b.i.d.) or 10 mg/kg b.i.d. methamphetamine throughout gestation, were examined at 30 days of age for changes in the monoamine system of their brains. 3. At the lower dose methamphetamine was neurotoxic to specific neuronal populations, mostly serotonergic. At the higher dose, methamphetamine retained its neurotoxic properties, but also stimulated the growth of axonal terminals in specific regions as evidenced by an increase in monoamine uptake sites. The neurochemical changes at the higher dose were correlated with deficits in adult behavioural measures. 4. Corresponding in vitro drug treatments of rat neuroblastomas cells also produced a dose-related effect on cellular growth and differentiation patterns. Neurotoxic as well as stimulatory effects of methamphetamine and some related compounds were seen in culture. 5. Our in vivo and in vitro observations demonstrate neurotoxic effects of amphetamines and the remodelling of synaptic morphology in response.

Amines↗
PubMed1995

Outcome assessment in depressed hospitalized patient.

Psychiatric symptoms as well as work, social, and physical functioning were compared in two groups of psychiatric patients (36 depressed only and 34 depressed in conjunction with an eating disorder) and 77 controls. In both groups, Global Assessment of Functioning (GAF) scores significantly improved from hospital admission to discharge and remained improved at 1.5 years postdischarge. As outpatients, the GAF, Zung Depression, and anxiety scores of both groups were significantly lower than for controls. Ratings of social functioning for depressed only outpatients did not differ from controls on five out of six measures. Predictors of posthospital improvement included high satisfaction with hospital treatment, high GAF scores on admission to hospital, perceived effectiveness of outpatient therapy, younger age, and an historical absence of sexual abuse or prior psychiatric hospitalization.

Activities of Daily Living↗
PubMed1994

A modified GAF scale.

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Activities of Daily Living↗
PubMed1993

In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring.

Chronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a regional increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open-field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine.

Animals↗
PubMed1992

Clinical and biochemical aspects of depressive disorders: III. Treatment and controversies.

The present document is the final of three parts of a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various treatments for depression, including psychotherapy, pharmacological, and somatic treatments, will be described in this third part. Also, some of the controversies in the field, as well as a summary of the most salient points of the review, will be discussed. Previous sections of this review dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders (Part I) and various transmitter/receptor theories of depressive disorder (Part II).

Antidepressive Agents↗
PubMed1991

Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques.

The present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Positron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field.

Depressive Disorder↗
PubMed1991

Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories.

The present document is the second of three parts in a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various receptor/transmitter theories of depressive disorders are discussed in this section. Specifically, data supporting noradrenergic, serotonergic, cholinergic, dopaminergic, GABAergic, and peptidergic theories, as well as interactions between noradrenergic and serotonergic, or cholinergic and catecholaminergic systems are presented. Problems with the data and future directions for research are also discussed. A previous publication, Part I of this review, dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders. A future publication, Part III of this review, discusses treatments for depression and some of the controversies in this field.

Animals↗
PubMed1991

Neurobiological evidence for epilepsy-induced interictal disturbances.

It is not in the best interest of persons with epilepsy to deny the possibility that seizures could cause enduring behavioral disturbances. Rather, it is essential to pursue clinical and animal investigations in order to identify any such changes that might occur and to elucidate their mechanisms. Many testable hypotheses can be developed from existing evidence. Antiepileptic medication may produce interictal behavioral disturbances in patients with epilepsy by indirect mechanisms. Some aberrant behaviors could be due to medication-induced systemic disorders, neuroendocrine dysfunction, or REM deficit, whereas depression following successful treatment with drugs, as well as with surgery, may be related more specifically to cessation of seizures. The underlying neuropathological process also induces neurological and mental deficits, but it is not always possible to differentiate those behavioral disturbances due to destructive effects of the lesion from those due to recurrent epileptic seizures. Behavioral disturbances are associated more frequently with epileptogenic lesions in limbic structures than with those elsewhere in the brain, but a relationship between hemispheric lateralization of the epileptogenic lesion and specific interictal behavioral symptoms remains controversial. When considering the effects of seizures per se on interictal behavior, it is important to realize that some "interictal" behavioral disturbances may actually be ictal events. Prolonged affective, autonomic, and psychic disturbances can occur in clear consciousness with unilateral limbic seizures that are not associated with scalp EEG changes. When epilepsy is acquired as a result of cerebral damage, the epileptogenic process takes time to develop before spontaneous seizures appear. It is more reasonable to assume that this progressive process continues than to postulate that it stops completely at the time the first seizure occurs. Epilepsy-induced protective homeostatic mechanisms that act to terminate ictal events, prevent ictal spread, and maintain the interictal state may also disrupt interictal function. Furthermore, seizures could indirectly influence interictal behavior as a result of their effects on neuroendocrine function and sleep. Because of confounding biological factors, it is difficult to document the association of any epilepsy disorder, by itself, with progressive behavioral disturbances in humans. Secondary epileptogenesis, protective homeostatic mechanisms, and epilepsy-induced disturbances in development can be readily demonstrated, however, in experimental animal models. In experimental animals, endogenous opoids are released during seizures and mediate some postictal behaviors. A physiological dependency on high levels of endogenous opioids released during seizures could produce depression as a withdrawal symptom interictally or when seizures no longer occur as a result of successful therapy. Experimental animal models of depression exist to test hypotheses concerning pro- and antidepressant effects of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Interictal changes in behavior and cerebral metabolism in the rat: opioid involvement.

Interictal changes in locomotor and shock-response behaviors were examined in rats that were kindled unilaterally or bilaterally in the amygdala. 2-Deoxyglucose and naloxone were used to test whether alterations in cerebral glucose metabolism or opioid functioning, respectively, correlated with changes in these behaviors. Bilaterally kindled rats, at 14 to 28 days after their last seizure, displayed increased locomotion (square crossing) in an open field compared with unilaterally kindled or control rats. Bilaterally kindled rats also showed elevated thresholds for the elicitation of a multiple squeak response to tail shocks. Single squeak or tail withdrawal responses to tail shock were not affected by bilateral kindling. Likewise, unilaterally kindled rats did not differ from controls on any of the behavioral measures. Naloxone (10 mg/kg, i.p.) reversed the increase in locomotion and elevation of multiple squeak thresholds in the bilaterally kindled rats. By itself, naloxone did not influence any of the behaviors. Finally, cerebral glucose metabolism was decreased, globally, in the forebrain of the bilaterally kindled rats, and naloxone normalized this change. Cerebral metabolism was not altered in unilaterally kindled rats compared with controls. Thus, changes in cerebral metabolism and opioid functioning may be involved in the mediation of interictal changes in locomotor and emotional behavior in rats.

Amygdala↗
PubMed1988

Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography.

14C-2-Deoxyglucose (2DG) was used to investigate changes in the rate of cerebral metabolism in 3 rat models of depressed behavior. The models had already been established in the literature and were induced by injections of alpha-methyl-para-tyrosine, withdrawal from chronic amphetamine, or stress. We verified that exploratory behaviors were depressed in each model and that an antidepressant drug, tranylcypromine, prevented the depressed behavior in each model. 2DG studies revealed that the rate of regional glucose metabolism was elevated bilaterally in the lateral habenula of each of the 3 models. Regional metabolic rates were reduced in each model in the dorsal medial prefrontal cortex, anterior ventral nucleus of the thalamus, and inferior colliculus. Forebrain global metabolic rates were also reduced in each of the models. Tranylcypromine prevented the elevated rate of lateral habenula metabolism seen in each of the models alone but did not significantly affect the rates of global metabolism. Our findings of identical metabolic changes in each of the models indicate that these changes are not idiosyncratic to a particular model; rather, they correlate with a generalizable state of depressed exploratory behavior in rats.

Amphetamine↗
PubMed1987

Limbic postictal events: anatomical substrates and opioid receptor involvement.

1. Amygdaloid kindled seizures in rats produce postictal motor deficits, disruption of affective responding to sensory input, postictal explosiveness, and seizure suppression that may be similar to events following complex partial seizures in humans. 2. Preliminary 2DG studies in kindled rats indicate that postictal motor deficits may be mediated by the substantia nigra. Disruption of affective responding and postictal seizure suppression may be mediated by the hippocampus. 3. Data from the literature indicates that postictal motor deficits may be mediated by mu and kappa opioid receptors. The disruption of affective responding may be mediated primarily be delta and maybe also by kappa receptors. Postictal explosiveness may involve either a non-mu receptor or it may be a non-opioid effect. Kindling-induced postictal seizure suppression may be mediated by kappa receptors and perhaps also by mu receptors. 4. Mechanisms underlying postictal effects of complex partial seizures in humans are suggested by the data in this manuscript. New approaches to the treatment of these postictal events are also proposed.

Animals↗
PubMed1986

Neurobiology of behavior: anatomic and physiological implications related to epilepsy.

Controversy exists concerning whether epileptic seizures can produce enduring alterations in neuronal function that cause interictal behavioral disturbances. Although arguments favoring the occurrence of epilepsy-induced disorders of behavior must not be presented in a way that adds to the stigmata associated with epilepsy, it is not in the best interest of epileptic patients to deny this possible relationship and overlook an opportunity to prevent or treat a major cause of disability. There is evidence to suggest that psychosocial factors cannot account for all the behavioral problems suffered by patients with epilepsy. Behavioral disturbances ascribed to antiepileptic drugs and specific structural lesions may also be due, in part, to epileptogenic mechanisms. Some interictal behavioral disturbances may actually reflect unrecognized ictal events. Most importantly, data obtained from clinical research and animal investigations suggest testable hypotheses of how recurrent epileptic seizures can alter neuronal function in ways that would predispose to specific disruptive interictal behaviors, such as aggression, depression and schizophrenia.

Aggression↗
PubMed1984

Activating endogenous opioid systems by electroconvulsive shock or footshock stress inhibits recurrent kindled seizures in rats.

Electroconvulsive shock (ECS) significantly decreased the behavioral manifestations of seizures elicited by amygdaloid stimulation in kindled rats. This anticonvulsant effect was significantly reduced by the opiate antagonist, naloxone, and by the development of morphine tolerance. A form of footshock stress known to cause opioid-mediated analgesia had a similar anticonvulsant effect, whereas another form causing non-opioid analgesia did not. These results suggest that the anticonvulsant effects of ECS and stress are mediated by the release of endogenous opioids.

Amygdala↗
PubMed1983

Changes in simple and complex behaviors following kindled seizures in rats: opioid and nonopioid medication.

To learn more about postictal behaviors and their underlying mechanisms, five behaviors and EEG recordings were studied following fully generalized, kindled seizures in rats. The behaviors included bar pressing for food; tail withdrawal, squeak, and multiple squeak responses to painful tail shocks; consumption of freely available food; clinging to a vertical grid; and locomotion. Latencies from the end of a seizure afterdischarge until each behavior recovered were compared and were found to cluster in three distinct pairs. Locomotion and grid clinging recovered most quickly; consumption of freely available food and EEG postictal depression recovered next; and bar pressing for food and the multiple squeak response recovered most slowly. Naloxone pretreatment (10 mg/kg but not 1 mg/kg) shortened recovery to multiple squeak responses, grid clinging, and locomotion, without affecting recovery of bar pressing, food consumption, or EEG postictal depression. These results suggest that complex behaviors recover more slowly following a seizure than simple behaviors. It also appears that opioids are released by a kindled seizure and mediate certain postictal changes in motor- and pain-related behaviors.

Animals↗
PubMed1982

Behavioral and electrographic effects of opioids on kindled seizures in rats.

Our laboratory previously suggested that opioid peptides are released by an amygdaloid kindled seizure and may affect the elicitation of a subsequent seizure. The present study examined the effects of morphine, naloxone, enkephalin analogues, and conditions of morphine tolerance and withdrawal on the severity and duration of a series of amygdaloid kindled seizures. The results suggest two distinct opiate/opioid actions on seizures. The first is an anticonvulsant effect on the behavioral manifestations of seizures. This effect is seen following a high dose (50 mg/kg) of morphine or a low dose (6 mg/kg) of enkephalin analogue (LY146104), and is reversed by naloxone. The second is a naloxone-reversible prolonging effect of the high dose of morphine on the electrographic components of the seizures. Receptor affinities of these various opiate/opioid drugs suggest that these two actions are mediated by different receptors which appear not to include high affinity mu receptors.

Animals↗