Search PubMed⌕ Search

Biomedical subjects

D J Nutt

Publications and source records attributed to D J Nutt.

266 records · Page 15Linked to original sources
PubMed1982

The anxiogenic action of benzodiazepine antagonists.

Two benzodiazepine antagonists were tested in an animal model of anxiety, the social interaction test. Ethyl beta-carboline-3-carboxylate (1 and 2 mg/kg) had a potent anxiogenic action; the imidazodiazepine RO 15-1788 (4-10 mg/kg) had a weak anxiogenic effect that with a larger dose (20 mg/kg) disappeared and RO 15-1788 (10 mg/kg) significantly counteracted the anxiogenic effect of the beta-carboline (1 mg/kg). The implications of these results for the understanding of the pharmacological basis of anxiety and for the existence and nature of an endogenous ligand for the benzodiazepine binding site are discussed.

Animals↗
PubMed1982

Comparison of the effects of repeated electroconvulsive shock on alpha 2- and beta-adrenoceptors in different regions of rat brain.

The effects of ten, once-daily electroconvulsive shocks on alpha 2 and beta-adrenoceptor binding were investigated in the rat cortex, hippocampus, hypothalamus and cerebellum. [3H]Clonidine and [3H]dihydroalprenolol were used as radioligands for alpha 2 and beta-adrenoceptors respectively. Twenty-four hours after the last shock, the density of beta-adrenoceptors was reduced in the cortex and hippocampus, but not in the hypothalamus or cerebellum. There was no change in the apparent affinity of the beta-receptors in any of the regions studied. Alpha 2-adrenoceptor density was reduced in all the regions studied (cortex, hippocampus, hypothalamus) with, again, no change in their apparent affinity. It is concluded that the effects of electro-convulsive shock on alpha 2 and beta-adrenoceptors show regional variation; possible reasons for this variation are discussed.

Animals↗
PubMed1981

Studies on the post-ictal rise in seizure threshold.

Seizure thresholds were determined by timed infusion of a convulsant drug. Following an electroconvulsive shock (ECS) rats exhibited a raised seizure threshold to infusion of the GABA antagonist drugs, pentylenetetrazol, bicuculline and isopropyl-bicyclophosphate, but not to the glycine antagonist strychnine or the 5-HT agonist, quipazine. The increase in threshold was seen following a bicuculline-induced seizure and 30 min following the last of a course of ECS given once daily for 10 days. The rise in seizure threshold still occurred when animals were pretreated with alpha-methyl-p-tyrosine (200 mg . kg-1), p-chlorophenylalanine (200 mg . kg-2), naloxone (1 mg . kg-1) or indomethacin (20 mg . kg-1). Diazepam (2 mg . kg-1), flurazepam (10 mg . kg-1) and sodium valproate (400 mg . kg-1) elevated basal seizure threshold and a further rise followed the ECS. Phenytoin (40 mg . kg-1) and carbamazepine (40 mg . kg-1) had no effect on basal seizure threshold or the ECS-induce rise. (¿Propranolol (20 mg . kg-1) did not affect basal seizure threshold but prevented the ECS-induced increase. The rise in seizure threshold following a convulsion may be an important adaptive mechanism which could be related to the reported increase in specific benzodiazepine binding following a seizure.

Animals↗
PubMed1981

Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats.

The mammalian central nervous system possesses specific high-affinity binding sites for the benzodiazepines and considerable evidence suggests that these binding sites are the pharmacological receptors through which these compounds act. Recently, ethyl beta-carboline-3-carboxylate (beta-CCE) has been identified in both human urine and rat brain. beta-CCE may be closely related to the endogenous ligand for the benzodiazepine receptor--it shows an affinity for the receptor of the same order as that of clonazepam, one of the most potent benzodiazepines, and is the first non-diazepinoid structure to be identified with an affinity in the nanomolar range. Furthermore, it is selective for the benzodiazepine receptor. Clinically and in animal studies, benzodiazepines have anti-convulsant, hypnotic and anxiolytic actions. We have therefore investigated whether beta-CCE exhibits any of these properties in rats. We report here that, in contrast to the benzodiazepines, beta-CCE lowers seizure threshold and reverses the sedative effect of flurazepam. If beta-CCE has a close structural relationship to the endogenous ligand, benzodiazepines may be antagonistic at the receptor site.

Animals↗
PubMedDate not supplied

Role of GABA in memory and anxiety.

This review assesses the parallel literature on the role of gamma-aminobutyric acid (GABA) in memory and anxiety. We review historical and new data from both animal and human experimentation which have helped define the key role for this transmitter in both these mental states. By exploring the overlap in these conditions in terms of pharmacology, brain circuitry, and clinical phenomenology, we begin to develop a theory that the two conditions are intrinsically interrelated. The role of GABAergic agents in dissecting out and demonstrating this interrelationship and in pointing the way to future research is discussed.

Animals↗
PubMedDate not supplied

Platelet binding studies in panic disorder.

Binding parameters of the alpha 2-adrenoceptor (using [3H]yohimbine) and the 5-HT uptake site (using [3H]imipramine) were measured in intact platelets in a group of 15 patients with a DSM-III diagnosis of panic disorder. When compared with an age- and sex-matched control population no differences in either Bmax or Kd were found. This result is discussed in light of the reports of platelet binding abnormalities in depression.

Adult↗
PubMedDate not supplied

Alpha-2-adrenoceptor control of cortisol and ACTH in normal volunteers: preliminary open trial of the effects of acute and chronic idazoxan.

To examine the role of alpha 2-adrenoceptors in the control of cortisol and ACTH, hormone responses to the selective alpha 2-antagonist idazoxan were studied in 12 normal volunteers. Plasma cortisol and ACTH were measured from 0930h-1230h on three occasions: before, on the 1st day, and on the 22nd day of an open treatment trial with idazoxan 40 mg administered three times per day. Compared with pretreatment cortisol levels, acute but not chronic idazoxan treatment attenuated the normal diurnal fall in plasma cortisol. Plasma ACTH concentrations were not altered by either dose of idazoxan. The attenuation of the diurnal fall in cortisol after acute idazoxan may be mediated through increased central availability of norepinephrine, and is similar to responses after high doses of the less selective alpha 2-antagonist yohimbine. Activity of central noradrenergic neurons appears to be reduced or normalized by chronic idazoxan, indicated by restoration of the normal diurnal fall in cortisol.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Association of short alleles of a VNTR of the serotonin transporter gene with anxiety symptoms in patients presenting after deliberate self harm.

The polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene consists of three alleles containing, respectively, 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. The frequencies of the three alleles in 384 individuals presenting after deliberate self harm were the same as a group of 346 controls. However, ratings of anxiety (and state anger) were higher in those patients with genotypes including the shorter repetitive elements. The findings support the hypothesis that, in this group of patients with low rates of severe psychiatric disorder, allelic variation in the serotonin transporter gene may contribute to the expression of anxiety symptoms.

Aggression↗
PubMedDate not supplied

[On the role of GABA in anxiety and depression].

Data on the role of gamma-aminobutyric acid (GABA) in pathogenesis of anxiety and depression are critically assessed. Clinical and experimental results indicative of an important role of GABA as the neurotransmitter involved in these mental states and their integration within a common pathogenic process are considered. The general neurochemical, pharmacological, and neurophysiological aspects of anxiety and depression are analyzed in the context of GABAergic system involvement in this process and the possibility of using GABAergic agents for the therapy of various related disorders.

Anxiety↗