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Biomedical subjects

K M Golden

Publications and source records attributed to K M Golden.

11 recordsLinked to original sources
PubMed2001

Combinations of clozapine and phencyclidine: effects on drug discrimination and behavioral inhibition in rats.

Phencyclidine (PCP) produces psychotomimetic effects in humans that resemble schizophrenia symptoms. In an effort to screen compounds for antipsychotic activity, preclinical researchers have investigated whether these compounds block PCP-induced behaviors in animals. In the present study, the atypical antipsychotic clozapine was tested in combination with an active dose of PCP in two-lever drug discrimination and mixed signalled-unsignalled differential-reinforcement-of-low-rates (DRL) procedures. PCP produced distinctive effects in each task: it substituted for the training dose in PCP discrimination and it increased the number of responses with short (<3 s) interresponse times as well as increasing overall response rates in the DRL schedule. Acute dosing with clozapine failed to alter the behavioral effects of PCP in either procedure even when tested up to doses that produced pharmacological effects alone. These results suggest that acute dosing with clozapine would not affect behaviors most closely associated with PCP intoxication. Further, they bring into question the utility of using PCP combination procedures in animals to screen for antipsychotic potential. Since chronic dosing is required for therapeutic efficacy of antipsychotics, future studies should focus on investigation of chronic dosing effects of these drugs in combination with PCP.

Animals↗
PubMed2001

Traumatic brain injury-induced changes in gene expression and functional activity of mitochondrial cytochrome C oxidase.

Traumatic brain injury (TBI) is documented to have detrimental effects on CNS metabolism, including alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. Studies on mitochondrial metabolism have also provided evidence for reduced activity of the cytochrome oxidase complex of the electron transport chain (complex IV) after TBI and an immediate (lhr) reduction in mitochondrial state 3 respiratory rate, which can persist for up to 14 days postinjury. Using differential display methods to screen for differences in gene expression, we have found that cytochrome c oxidase II (COII), a mitochondrial encoded subunit of complex IV, is upregulated following TBI. Since COII carries a binding site for cytochrome c in the respiratory chain, and since it is required for the passage of chain electrons to molecular oxygen, driving the production of ATP, we hypothesized that metabolic dysfunction resulting from TBI alters COII gene expression directly, perhaps influencing the synaptic plasticity that occurs during postinjury recovery processes. To test this hypothesis, we documented COII mRNA expression and complex IV (cytochrome c oxidase) functional activity at 7 days postinjury, focusing on the long-term postinjury period most closely associated with synaptic reorganization. Both central fluid percussion TBI and combined TBI and bilateral entorhinal cortical lesion were examined. At 7 days survival, differential display, RT-PCR, and Northern blot analysis of hippocampal RNA from both TBI and combined insult models showed a significant induction of COII mRNA. This long-term elevation in COII gene expression was supported by increases in COII immunobinding. By contrast, cytochrome oxidase histochemical activity within tissue sections from injured brains suggested a reduction of complex IV activity within the TBI cases, but not within animals subjected to the combined insult. These differences in cytochrome c oxidase activity were supported by in vitro assay of complex IV using cerebral cortical and hippocampal tissues. Our present results support the hypothesis that COII is selectively vulnerable to TBI and that COII differences may indicate the degree of metabolic dysfunction induced by different pathologies. Taken together, such data will better define the role of metabolic function in long-term recovery after TBI.

Animals↗
PubMed2000

Separation of drug effects on timing and behavioral inhibition by increased stimulus control.

Impulsive behavior may represent, in part, a failure of behavioral inhibition (the ability to delay or inhibit a response). In this study, use of a multiple signaled-unsignaled differential-reinforcement-of-low-rates (DRL) 15-s schedule allowed examination of drug effects in conditions in which level of stimulus control differed. Results showed that whereas diazepam increased premature responding during signaled and unsignaled DRL components, amphetamine and delta9-tetrahydrocannabinol increased premature responding primarily during unsignaled components when timing was necessary for efficient performance on the task. In contrast, pimozide and desipramine increased long-delay responses across both components, resulting in longer mean interresponse times. Collectively, these results suggest that the use of different levels of stimulus control may aid in separation of drug effects on timing and other behavioral processes, including behavioral inhibition.

Amphetamine↗
PubMed1997

Effects of modulation of nitric oxide on acoustic startle responding and prepulse inhibition in rats.

The nitric oxide-arginine pathway is intimately connected to the release of dopamine and glutamate, two neurotransmitter systems that may be dysfunctional in schizophrenia. In addition, nitric oxide synthase inhibitors share several behavioral effects with the psychotomimetic drug, phencyclidine. Previous research has found that phencyclidine-like drugs disrupt prepulse inhibition of the acoustic startle response, an animal model of sensorimotor gating, an attentional process that is disrupted in certain neuropsychiatric disorders in humans (e.g., acute schizophrenia). The purpose of the present study was to examine the effects of nitric oxide modulators in this model. Following injection with a nitric oxide modulator or phencyclidine, rats were placed in startle chambers in which they were exposed to acoustic pulses presented alone or preceded by a prepulse. As in previous reports, phencyclidine disrupted prepulse inhibition at doses that did not affect startle during pulse alone trials. In contrast, the nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (L-NOARG) and N(G)-nitro-L-arginine methyl ester (L-NAME), dose-dependently decreased startle during pulse alone trials, but neither drug affected prepulse inhibition. A nitric oxide precursor, L-arginine, produced similar results. Sodium nitroprusside (a nitric oxide releaser) and 7-nitroindazole (a third nitric oxide synthase inhibitor) did not affect startle amplitudes during pulse alone or prepulse + pulse trials. The present results suggest that modulation of nitric oxide synthesis or availability does not disrupt sensorimotor gating of the acoustic startle response and is probably not involved in mediation of this type of attentional deficit in humans.

Acoustic Stimulation↗
PubMed1997

Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoroanandamide in rhesus monkeys.

In previous research arachidonylethanolamide (anandamide) has been shown to produce behavioral effects in mice characteristic of psychoactive cannabinoids, including antinociception, catalepsy, hypothermia, and hypomotility. However, differences have also been found between anandamide and delta9-tetrahydrocannabinol (delta9-THC), with anandamide having lower potency, a more rapid onset, and shorter duration of action than delta9-THC. Although it can produce delta9-THC like discriminative stimulus effects in rats, anandamide also produces concomitant response rate decreasing effects, whereas with delta9-THC there is a better separation of these two behavioral effects. The present study was designed to examine the discriminative stimulus effects of anandamide in rhesus monkeys trained to discriminate delta9-THC from vehicle. While anandamide failed to produce reliable substitution for delta9-THC and did not reduce response rates at doses up to 10 mg/kg, 2-methylarachidonyl-2'-fluoroethylamide (methylated fluoroanandamide), a putative stable analog of anandamide, produced full dose-dependent substitution for delta9-THC at doses that caused no significant changes in response rates. These results suggest that systemically administered anandamide may be metabolized in monkeys before behaviorally active concentrations could reach the brain and further suggest that the metabolically more stable analog of anandamide, methylated fluoroanandamide, may aid in the discovery of functional properties of the endogenous cannabinoid system.

Analgesics↗
PubMed1978

The multiproblem patient. A goal-oriented approach.

With greater accessibility of patients from lower socioeconomic backgrounds to medical care, the physician in private or clinical practice is increasingly confronted with patients whose medical problems either become quickly overshadowed by or entwined with seemingly hopeless socioeconomic or legal problems. Traditionally, these patients have sought help in charity hospitals and emergency rooms that are staffed with social workers, rehabilitation counselors, and other trained personnel who could deal with problems that were not specifically medical. As accessibility to physicians in private or clinical practice increases, the need for specific techniques in working with persons from this population becomes critical.

Attitude of Health Personnel↗
PubMed1978

Suicide assessment: a clinical model.

One of the most critical and ill-defined areas of the physican's practice is the evaluation of suicidal intent, particularly of the patient who has made no previous such attempts. Making the problem more complex is the attitude of the physician toward the self-destroyer, as determined by his/her upbringing and training. This article first confronts the issue of how the attitude of the physician can and does affect the potentially suicidal patient. Secondly, a conceptual model for a suicide evaluation is presented. This model has been designed for flexibility and practicality in order to help ensure that a complete evaluation can be done within the requirements and necessities of the practicing physician.

Attitude of Health Personnel↗
PubMed1977

Psychiatry. The physician as family therapist.

Patients or families with emotional problems often ask for help or come to the physician's attention in other ways. For those with long-standing or severe problems, referral to an appropriate mental health resource is indicated. Many, however, are simply involved in situational upsets which have temporarily overwhelmed the family's ability to resolve problems. For these families, the physician can be an effective family therapist. Problems can often be dealt with quickly and successfully without disruption of normal office routine. Basic to the physician's providing effective help are knowledge of the effects of childhood experiences on later interactions within a family and honest self-evaluation as to ability and interest in undertaking family therapy.

Child, Preschool↗
PubMed1977

Voodoo in Africa and the United States.

The authors states that the practice of hexing is not just a nearly extinct phenomenon of isolated rural communities of the deep south of the United States but is evident in large urban areas in the northeast and west. He describes the psychological mechanisms of voodoo as practiced in West Africa to provide insight into similar practices in the United States.

Africa, Western↗
PubMed1975

Tandem psychotherapy: a model for rotating student therapists.

Student psychotherapists often spend relatively brief periods in clinical placements or rotations. In this article, Lewis R. Wolberg's model for short-term therapy is extended and adapted for use in long-term treatment by multiple student therapists treating patients in tandem. Techniques are proposed to enhance continuity of therapy and smooth changing of therapists.

Comprehensive Health Care↗