Showing papers by "Angela Clow published in 2011"
TL;DR: A comparison of the activity of five substituted benzamide drugs in the in vitro models of dopamine receptor activity with their ability to induce catalepsy and to inhibit apomorphine-induced stereotyped behaviour concludes that these compounds act on the cerebral dopamine pathways in a manner which differs from that of classical neuroleptics.
Abstract: Cerebral dopamine receptor antagonism in vivo is associated with the ability to interact with two in vitro models of these receptors. Thus the ability to inhibit dopamine stimulation of the adenylate cyclase from rat striatum has been suggested as a model of post-synaptic dopamine receptor activity and of neuroleptic potential (Clement-Cormier, Kebabian & others, 1974; Miller, Horn & Iversen, 1974). Similarly, the ability to displace radioactive ligands from their binding sites in rat striatal preparations is also used as an index of an interaction with post-synaptic dopamine receptors and of neuroleptic activity (Seeman, Chau-Wong & others, 1975; Creese, Burt & Snyder, 1976). This latter model is believed to provide a better correlation between in vivo clinical neuroleptic activity and in vitro activity than the adenylate cyclase system. We have previously reported that some substituted benzamide drugs, such as metoclopramide and sulpiride, exhibit behavioural and biochemical properties associated with a blockade of cerebral dopamine receptors (Dolphin, Jenner & others, 1975; Peringer, Jenner & Marsden, 1975; Peringer, Jenner & others, 1976; Elliott, Jenner & others, 1977). Such compounds to a variable degree block apomorphine-induced locomotor activity, inhibit apomorphine-induced circling in rodents with unilateral nigrostriatal lesions, and elevate striatal and mesolimbic concentrations of the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). We have, however, been unable to demonstrate a significant effect of these compounds on the dopamine stimulation of the adenylate cyclase from rat striatum. This, and other data, has led us to conclude that these compounds act on the cerebral dopamine pathways in a manner which differs from that of classical neuroleptics. The present study is a comparison of the activity of five substituted benzamide drugs in the in vitro models of dopamine receptor activity with their ability to induce catalepsy and to inhibit apomorphine-induced stereotyped behaviour, these behavioural tests being chosen since they are often used to screen neuroleptic activity. These data are then compared with the
123 citations
TL;DR: During the short post-awakening period, an exception exists to the generally pertaining association between higher levels of cortisol and poorer cognitive performance, and the pattern of results across different cognitive tests suggests an association between cortisol and those domains of cognitive functioning which depend crucially on the integrity of the hippocampus and pre-frontal cortex.
77 citations
TL;DR: This cross-sectional study indicates that, despite consistent associations between the CAR and indices of trait-like cardiovascular activity, the CAR is not related to concurrent changes of cardiac autonomic activation following awakening.
63 citations
TL;DR: Findings indicate that the same pattern of cortisol dysregulation associated with disorder in adulthood manifests as a function of anxious (but not avoidant) insecure attachment style in females during healthy childhood and adolescence.
Abstract: Background: Attachment style has been linked with basal cortisol secretion in healthy adult women. We investigated whether dysregulation in basal cortisol secretion may be evident in younger healthy females.
Methods: Sixty healthy females aged 9–18 years (mean 14.16, SD ± 2.63 years) participated in the Attachment Style Interview (ASI). Eight saliva samples, synchronised to awakening, were collected per day on two consecutive weekdays to examine the cortisol awakening response (CAR) and the subsequent diurnal decline.
Results: Participants exhibiting an anxious attachment style had higher cortisol levels on awakening, in contrast to those who were securely attached. The anxious insecure group also showed an attenuated CAR compared to all other participants. Attachment style groups did not differ in cortisol secretion over the remainder of the day.
Conclusions: These findings indicate that the same pattern of cortisol dysregulation associated with disorder in adulthood
62 citations
TL;DR: During the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls, contributing to the understanding of the physiology of SAD.
47 citations
TL;DR: The data suggest that the central pharmacological activity of sulpiride and sultopride resides in the (‐)‐enantiomers and that this activity occurs at cerebral dopamine receptors not dependent on adenylate cyclase for functional activity.
Abstract: Apomorphine-induced locomotor activity in reserpine-pretreated mice was antagonized by pretreatment with (-)-sulpiride and (-)-sultopride. The (+)-enantiomers were inactive. Apomorphine- and amphetamine-induced stereotyped behaviour in rats were antagonized by (-)-sultopride but not by the (+)-enantiomer. Neither enantiomer of sulpiride prevented the onset of the stereotyped response. Both (-)-sulpiride and (-)-sultopride induced increases in striatal and mesolimbic HVA and DOPAC concentrations; (+)-sultopride elevated striatal and mesolimbic DOPAC concentrations but not HVA, while (+)-sulpiride had no effect on HVA or DOPAC in either area. Dopamine concentrations were reduced by the enantiomers of sultopride but not by sulpiride. Low concentrations (10−9 −10−66 M) of the (-)-enantiomers of both drugs displaced [3 H]spiperone from its specific binding site in rat striatal preparations, but the (+)-enantiomers were 40 and 100 times less active. However, neither enantiomer of either drug anatagonized the dopamine-induced stimulation of adenylate cyclase in rat striatal preparations. The data suggest that the central pharmacological activity of sulpiride and sultopride resides in the (-)-enantiomers and that this activity occurs at cerebral dopamine receptors not dependent on adenylate cyclase for functional activity.
39 citations
TL;DR: Another model dependent upon enhanced dopamine-like activity, namely the apomorphine-induced circling behaviour observed in mice with unilateral 6-hydroxydopamine lesions of the striatum is studied, suggesting that the capacity of propranolol to antagonize some, but not all, dopamine-mediated behaviours was not due to its 8-blocking actions.
Abstract: The suggestion that (&)-propranolol might be valuable in treating schizophrenia (Yorkston et al 1974) has led to biochemical (Sullivan et a1 1972; Fuxe et al 1976; Wiesel 1977) and behavioural studies (Costall et al 1978) into its effects on central catecholaminergic systems. Costall et al(l978) investigated the effects of a range of doses (2.540 mg kg-l) of (&)-propranolol and its (+)and (-)-isomers upon the following dopamine-dependent motor behaviours: the induction of dyskinetic phenomena in the guinea-pig by intrastriatal dopamine agonists, rat hyperactivity due to the injection of dopamine into the nucleus accumbens, and mouse climbing behaviour induced by apomorphine. Only the latter two behaviours were antagonized by propranolol, and the (-)-isomer, which is the potent p-receptor antagonist, was less effective than the relatively inactive (+)-isomer. That result suggested that the capacity of propranolol to antagonize some, but not all, dopamine-mediated behaviours was not due to its 8-blocking actions. We have studied another model dependent upon enhanced dopamine-like activity, namely the apomorphine-induced circling behaviour observed in mice with unilateral 6-hydroxydopamine lesions of the striatum. 6-Hydroxydopamine (16 pg in 4 ~ 1 0 . 9 % saline) was injected directly into the right striatum according to the method of Pycock et al (1975). Two months after surgery, circling behaviour in mice was observed in individual boxes (12cm x 12cm). The number of net complete turns to the left was recorded within a 1 min period 15 min after apomorphine (0.5 mg kg-' s.c.) administration. Mice were pretreated 60 min earlier with saline or a propranolol isomer ((*) 1-50 rng kg-*; (+) and (-) 25 mg kg-l, all i.p.). The results are summarized in Table 1. (&)-Propranolol antagonized apomorphine-induced turning in a dose-dependent manner. (+)-propranolol (25 mg kg-') inhibited apomorphine-induced circling to the Same extent as (-)-propranolol or (5)-propranolol gven in the same dose. At this dose there were signs of sedation, muscular hypotonia (Leszkovszky & Tardos 1965) and hyporeactivity (Bainbridge & Greenwood 1971) which became more marked at 50mg kg-l. (A11 the mice given 100 mg kg-l (*)-propranolol subsequently died.) Fuxe et a1 (1976), who injected
10 citations
TL;DR: Supplements of hydrocortisone do not reduce the desire to smoke but may ameliorate withdrawal-related depression and anxiety, although the clinical benefit is slight.
Abstract: Many smokers experience a decline in cortisol to sub-normal levels during the first days of smoking cessation. A greater decline in cortisol is associated with more intense cigarette withdrawal symptoms, urge to smoke and relapse to smoking. Findings from an uncontrolled study suggest that glucocorticoids could ameliorate cigarette withdrawal. We investigated whether taking oral hydrocortisone would reduce withdrawal symptoms and the desire to smoke on the first day of temporary smoking abstinence compared with placebo. Using a double-blind within-subject randomised crossover design, 48 smokers took a single dose of 40 mg hydrocortisone, 20 mg hydrocortisone or placebo following overnight smoking abstinence. Abstinence was maintained through the afternoon, and withdrawal symptoms and the desire to smoke were rated across the morning. Salivary cortisol was assessed in the afternoon prior to abstinence (baseline) and while abstinent after each treatment. There was a significant dose–response relation between dose of hydrocortisone and reduction in depression and anxiety ratings while abstinent, but there were no other statistically significant associations with dose. Overall, the decline in cortisol following smoking cessation (placebo only) was not significant. Cortisol level on the afternoon of smoking abstinence was not significantly associated with symptom ratings. Supplements of hydrocortisone do not reduce the desire to smoke but may ameliorate withdrawal-related depression and anxiety, although the clinical benefit is slight.
2 citations