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D C Roberts

Publications and source records attributed to D C Roberts.

At least 109 records · Page 6Linked to original sources
PubMed1987

The effect of haloperidol on cocaine self-administration is augmented with repeated administrations.

Administration of haloperidol (0.075 mg/kg) prior to a 4-h self-administration session increases cocaine intake by male rats. Animals pretreated daily with haloperidol showed a significant augmentation of this response, with cocaine intake climbing from 37% above baseline to 65% above baseline in 7 days. Control rats given two treatments of haloperidol 7 days apart showed no augmentation of the response. This increased drug effect is unusual, since most behavioral actions of haloperidol in laboratory animals show tolerance. In humans, the antipsychotic activity of neuroleptic drugs requires many days to develop. Cocaine self-administration behavior might therefore provide a model for antipsychotic drug action.

Animals↗
PubMed1987

Increased self-administration of cocaine following haloperidol: effect of ovariectomy, estrogen replacement, and estrous cycle.

Rats which have been trained to self-administer cocaine intravenously show a dose-dependent increase in drug intake when pretreated with dopamine antagonists. This neuroleptic-induced increase in cocaine intake may be related to the antipsychotic potency and suggests that self-administration behavior may provide a useful model for evaluating neuroleptic activity. The present study examines the influence of ovarian hormones on the potency of the neuroleptic haloperidol using the cocaine self-administration model. It was found that the potency of haloperidol fluctuated across the estrous cycle with subjects in diestrus self-administering more cocaine than animals tested in estrus or proestrus. It was also demonstrated that the potency of haloperidol was reduced significantly following ovariectomy (OVX), however this OVX-induced attenuation could not be reversed with a number of estrogen or catechol-estrogen treatments. To the extent that the self-administration model can reflect the potency of antipsychotic drugs, these data indicate that ovarian function can affect neuroleptic activity, although the hormone(s) involved remain unclear. The clinical implications of these data underscore the need to further examine the influence of female sex hormones on the therapeutic efficacy of antipsychotic drugs.

Animals↗
PubMed1987

Causal chunking: memory and inference in ongoing interaction.

We propose that people simplify their perceptions of their interactions by organizing them into discrete casual chunks. Once formed, these chunks presumably influence the extent to which people are aware of their influence on others, as well as their impressions of others. We anticipated that people would form self-causal chunks (e.g., my action causes my partner's action) when they possessed an offensive set and other-causal chunks when they possessed a defensive set. We also expected that a self-causal chunking strategy would make salient people's influence on their partners and thereby discourage them from concluding that their partner's behaviors reflected underlying dispositions. In contrast, we anticipated that an other-causal chunking strategy would obscure people's influence on their partners, thereby encouraging them to infer that their partners' behaviors reflected underlying dispositions. We tested these hypotheses by inducing participants to develop either a defensive or an offensive set prior to interacting with another person in a simulated arms race. After the interactions, we assessed the manner in which participants chunked their interactions, as well as their impressions of partners. The results supported our predictions. The implications of these findings for understanding conflict and misunderstanding in interpersonal relations are discussed.

Adult↗
PubMed1987

The importance of the non-protein components of the diet in the plasma cholesterol response of rabbits to casein. Zinc and copper.

To characterize further the effect of protein-mineral interaction on plasma cholesterol, four groups of rabbits were placed on cholesterol-free, semi-purified diets for 12 weeks. The diets were similar in proximate composition with either casein or soya-bean protein isolate as the protein source (250 g/kg). The dietary zinc content of the casein diets was increased to 22 mg/kg to equal that of the soya-bean diets. The copper content was set at 2 and 6 mg/kg. There were no differences in weight gain; all animals grew at a similar rate. When the dietary Zn content was equalized, the plasma and liver cholesterol responses were similar regardless of the source of protein. Differences in liver Cu and Zn were observed. As dietary Cu increased, Cu decreased and Zn increased in the liver. Hepatic Zn was also higher in soya-bean-fed than in casein-fed animals. No effects on plasma Cu and Zn were seen. The addition of Zn to the casein diet resulted in a similar plasma cholesterol to that of animals fed on the soya-bean diet, suggesting that casein-induced hypercholesterolaemia is due to a marginal Zn intake.

Animals↗
PubMed1986

Increased self-administration of cocaine following haloperidol: sex-dependent effects of the antiestrogen tamoxifen.

Intravenous self-administration of cocaine is extremely sensitive to the effects of antipsychotic drugs, making this behavior a useful screen for neuroleptic potency. A possible interaction between female sex hormones and antipsychotic activity was investigated, using increased rates of cocaine self-administration as a measure of neuroleptic action. We found that female rats were more sensitive to haloperidol than were male rats. Female rats treated with a single injection of the antiestrogen tamoxifen 24 hr prior to test showed a significantly reduced response to haloperidol. The normal response was found to have recovered by one week following the tamoxifen treatment. Tamoxifen had no significant effect in male rats. These data, along with previous observations, indicate that ovarian function can greatly influence the behavioral response to antipsychotic drugs. To the extent that the self-administration model may reflect the potency of an antipsychotic drug, these data may indicate that female rats are more sensitive to the activity of neuroleptic drugs. Secondly, pretreatment with tamoxifen results in a significant attenuation of the activity of haloperidol.

Animals↗
PubMed1985

An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro.

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. . pmol-1 (46 d.p.m. . ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.

Carbon Radioisotopes↗
PubMed1985

Evidence on the retrograde neurotoxicity of doxorubicin.

Doxorubicin, a fluorescent retrograde neurotoxin, killed neurons in the ventral tegmentum and thalamus that were afferent to the injection site in the caudate-putamen. The neurotoxic effects in the ventral tegmentum and thalamus were prevented by a large coronal knife cut caudal to the injection site in the striatum, suggesting that retrograde transport of doxorubicin is necessary for the death of afferent neurons. In the striatum the neurotoxic effects of doxorubicin 14 days post-injection were quantitatively much greater on afferent neurons (as assessed by a 72% drop in dopamine levels) than on local striatal perikarya (as evidenced by the small 22% drop in the activity of glutamic acid decarboxylase). Doxorubicin may be a useful tool for selectively destroying, by way of retrograde transport, neurons that are afferent to a site in the brain.

Animals↗
PubMed1985

Supersensitivity to the anticonvulsant and proconvulsant activity of clonidine following noradrenaline depletion induced by 6-hydroxydopamine.

Electrically induced focal cortical seizures were examined in 6-hydroxydopamine (6-OHDA) pretreated or control rats in the presence of 0, 1, 2.5, 5, and 10 micrograms/kg clonidine. In baseline determinations, rats pretreated with 6-OHDA showed lower seizure thresholds and longer behavioral and electrographic seizure than controls. Consistent with other reports, the lowest dose of clonidine (1 microgram/kg) inhibited seizures in control animals; 6-OHDA potentiated the anticonvulsant effect of the lowest dose of clonidine but exacerbated seizure in the presence of the highest dose of clonidine (10 micrograms/kg). Since others have reported proconvulsant effects of clonidine at much higher doses (100 or 1,000 micrograms/kg) using control animals, the depletion of forebrain norepinephrine with 6-OHDA therefore appears to produce a supersensitivity both to the proconvulsant and to the anticonvulsant effect of clonidine. These data suggest that the receptors that mediate the proconvulsant (possibly alpha 1 adrenoceptors) and the anticonvulsant (possibly alpha 2 adrenoceptors) effects are located postsynaptically.

Animals↗
PubMed1985

Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens.

In previous experiments we have demonstrated that bilateral infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens result in a drastic reduction in the rate of cocaine self-administration. If this effect is due to the destruction of a presynaptic dopaminergic element in this nucleus, then selective removal of the postsynaptic neuron should also disrupt cocaine self-administration. This hypothesis was tested using the neurotoxin kainic acid. Bilateral kainic acid infusions into the nucleus accumbens resulted in a drastic destruction of cell bodies yet did not damage catecholamine innervation in areas anterior to the accumbens. The effects of these kainic acid infusions were evaluated in rats that had previously acquired cocaine self-administration behavior. These lesions were found to severely disrupt cocaine intake and the degree of damage produced in the accumbens was found to correlate (r = 0.88) with postlesion cocaine intake. These lesions were additionally found to disrupt apomorphine and heroin self-administration. The possibility that these results are due to destruction of systems necessary for stimulant and opiate reward is discussed.

Animals↗
PubMed1985

The importance of the non-protein components of the diet in the plasma cholesterol response of rabbits to casein.

To characterize the hypercholesterolaemic effect of casein further, four groups of young male rabbits in two separate experiments were placed on cholesterol-free semi-purified diets for 12 weeks. The diets were similar in composition, with either casein or soya-bean-protein isolate providing the protein source (250 g/kg). In two of these diets the salt mix was reduced by 45% (normally 40 g/kg) and replaced by potassium bicarbonate. Growth was unaffected by these alterations in dietary salts except for one group given the soya-bean-reduced-salts diet. The mean concentrations of plasma cholesterol were significantly higher in all casein-fed groups as compared with their soya-bean-fed counterparts but the response was much greater in those given the casein-reduced-salts diet. Contrary to expectations, analysis of the diets showed the zinc and copper concentrations of the casein diets to be less than those of the soya-bean diets. This was due to the greater concentrations of Cu (threefold) and Zn (twofold) in the soya-bean-protein isolate compared with casein. The mean concentration of Zn in fur was significantly decreased in casein-fed rabbits and these animals also excreted less Zn but more Cu in their urine than those given the casein-reduced-salts diet. The rabbits given the casein diet with the least salt mix showed the greatest degree of hypercholesterolaemia, suggesting an interaction between trace elements and the casein effect.

Animals↗
PubMed1985

Relationship between levels and uptake of serotonin and high affinity [3H]imipramine recognition sites in the rat brain.

High affinity [3H]imipramine binding, endogenous levels of serotonin and noradrenaline, and serotonin uptake were determined in brain regions of rats with selective destruction of serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), of adrenergic neurons by 6-hydroxydopamine (6-OHDA), and of rats treated with reserpine. Neonatal treatment with 5,7-DHT resulted in a significant decrease of both serotonin levels and density (Bmax) of high affinity [3H]imipramine binding sites in the hippocampus. In contrast, an elevation of serotonin levels and an increase in Bmax of [3H]imipramine binding were noted in the pons--medulla region. No changes were observed in the noradrenaline content in either of these regions. Intracerebral 6-OHDA lesion produced a drastic suppression of noradrenaline levels in cerebral cortex but failed to alter the binding affinity (KD) or density (Bmax) of [3H]imipramine recognition sites. A single injection of reserpine (2.5 mg/kg) resulted in marked depletion of both serotonin (by 57%) and noradrenaline (by 86%) content and serotonin uptake (by 87%) in the cerebral cortex but had no significant influence of the parameters of high affinity [3H]imipramine binding in this brain region. The results suggest that high affinity [3H]imipramine binding in the brain is directly related to the integrity of serotonergic neurons but not to the magnitude of the uptake or the endogenous levels of the transmitter, and is not affected by damage to noradrenergic neurons or by low levels of noradrenaline.

5,7-Dihydroxytryptamine↗
PubMed1984

Corticosterone prevents the increase in noradrenaline-stimulated adenyl cyclase activity in rat hippocampus following adrenalectomy or metopirone.

Corticosterone modulation of the noradrenaline-responsive cyclic AMP generating system was examined in rat hippocampus. Adrenalectomy was found to produce a small but significant elevation in the rate of cyclic AMP formation in response to noradrenaline. Implantation of corticosterone pellets 5 days prior to sacrifice prevented this adrenalectomy-induced increase. Metopirone, an inhibitor of corticosterone synthesis, was also observed to increase cyclic AMP formation. This elevation was seen 2 h following a 50 mg/kg i.p. injection and was completely prevented by corticosterone pellet implantation. Metopirone had no significant effect on cyclic AMP production after 1 h, while a slight but statistically non-significant elevation remained at 4 h. These observations parallel the inhibitory effect of Metopirone on corticosterone synthesis as determined by serum corticosterone levels.

Adenylyl Cyclases↗
PubMed1984

Atypical neuroleptics increase self-administration of cocaine: an evaluation of a behavioural screen for antipsychotic activity.

Several drugs have been shown to exert antipsychotic effects, yet they display an atypical profile with respect to standard neuroleptic drug screens. Low doses of traditional neuroleptics are known to increase self-administration of psychomotor stimulants; we sought to determine whether these atypical drugs would cause a comparable effect. Sulpiride, metoclopramide and thioridazine produced a dose-dependent increase in cocaine intake similar to that found for chlorpromazine, haloperidol, pimozide and flupenthixol. This effect was found to correlate (r = 0.94) with daily clinical dose. Clozapine, however, produced a dose-dependent decrease in cocaine intake. The advantages and disadvantages of using this measure as a screening procedure for neuroleptic drugs are discussed.

Animals↗
PubMed1984

Neonatal 6-hydroxydopamine prevents adaptation to chemical disruption of the pituitary-adrenal system in the rat.

Three days after the subcutaneous implant of a dexamethasone pellet, which depletes both corticosterone and ACTH, normal rats showed impaired acquisition of a two-way avoidance task. Rats who had received systemic 6-hydroxydopamine at birth to lesion the forebrain noradrenergic terminals from the locus coeruleus did not show this impairment. After a single injection of metyrapone, which inhibits corticosterone synthesis and increases ACTH release, both intact and norepinephrine (NE)-depleted rats showed impaired avoidance acquisition. After the seventh injection, however, acquisition in normal rats was no longer impaired by the drug while the NE-depleted rats were still deficient. These results indicate that the simple combination of forebrain NE loss with reduced corticosterone levels does not necessarily retard avoidance acquisition. Rather, they suggest that the NE efferents from the locus coeruleus are essential for the brain's adaptation to at least some behavioral consequences of changes in the circulating level of ACTH.

Adrenocorticotropic Hormone↗