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Biomedical subjects

D C Roberts

Publications and source records attributed to D C Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1994

A single injection of either flupenthixol decanoate or haloperidol decanoate produces long-term changes in cocaine self-administration in rats.

The effect of decanoate forms of flupenthixol and haloperidol on cocaine self-administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability.

Animals↗
PubMed1994

Neuroleptics block high- but not low-dose heroin place preferences: further evidence for a two-system model of motivation.

The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brainstem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results.

Animals↗
PubMed1994

Decreased bone mineral density in children with phenylketonuria.

Previous studies have suggested that children with phenylketonuria (PKU) have a reduction in bone mineralization compared with control subjects. To investigate this, bone mineral density (BMD) of the total body (TBMD) was measured in 32 prepubertal children with PKU and in 95 age-matched control subjects. Spine bone mineral density (SBMD) was also recorded in a subset, 24 with PKU and 55 control subjects. The effect of dietary intake on bone mass was assessed in 30 of the children with PKU and in 12 control subjects. In the children with PKU, TBMD and SBMD were significantly lower than in the control subjects after adjustment for height and weight (P = 0.03 and P = 0.003, respectively). The children with PKU had a higher intake of calcium (P < 0.0001), phosphorus (P = -0.0002), and magnesium (P < 0.0001), suggesting that their lower BMD occurred despite an adequate diet based on current recommendations. Further study is needed to establish the cause of this deficit in bone mass and the benefit of additional nutritional support to reverse this problem.

Absorptiometry, Photon↗
PubMed1994

Ultrastructure of ostrich (Struthio camelus) spermatozoa. II. Scanning electron microscopy.

The three-dimensional structure and size of ostrich sperm is unknown. In this study, the morphology and dimensions of ostrich sperm were determined by scanning electron microscopy of semen samples obtained from sexually mature males during the breeding season. The results indicate that sperm cells of the ostrich are of the sauropsid type characteristic of non-passerine birds and, in general appearance, resemble those of the chicken, turkey, guinea fowl, budgerigar and tinamou. They differ from tinamou sperm, however, in that they do not show a small bump at the tip of the acrosome. Ostrich sperm are shorter (69.6 microns total length) than those of the chicken, turkey and guinea fowl, but longer than those of the budgerigar. A lack of information makes it impossible to compare the dimensions of ostrich sperm with those of other ratites such as the rhea. In ostrich and guinea fowl, the sperm head is proportionately longer than that of the chicken, turkey and budgerigar as determined by tail to head ratios. Two distinct groups of ostriches could be distinguished on the basis of differences in the length of various sperm cell components. This may reflect persistent genetic (subspecies) variations in the domestic ostrich population.

Animals↗
PubMed1993

Dopaminergic antagonism within the nucleus accumbens or the amygdala produces differential effects on intravenous cocaine self-administration under fixed and progressive ratio schedules of reinforcement.

Bilateral intracerebral injections of the D1 receptor antagonist, SCH 23390, were administered into the nucleus accumbens (NACC) or amygdala (AMY) immediately prior to an i.v. cocaine self-administration session. Injection into both sites produced a dose-dependent (0.1-2.0 micrograms/injection) increase in the rate of cocaine self-administration under a fixed ratio (FR) schedule of reinforcement (1.5 mg/kg/injection). However, injection into the AMY produced a significantly greater increase in rate of drug intake than within the NACC. In contrast, under a progressive ratio (PR) schedule of cocaine reinforcement the D1 antagonist had very little effect within the AMY on break point (BP) but greatly reduced the BP following injection into the NACC. A locomotor activity study revealed that following systemic injection of cocaine (10 mg/kg i.p.), SCH 23390 (1.0 microgram/injection site) significantly reduced activity to comparable levels following injection into either brain site. This indicates that the dissociation of effects between the two neural sites within the cocaine self-administration paradigm does not appear to be due to greater locomotor reducing actions of the antagonist within the NACC. These results demonstrate that a significant contribution is made by AMY dopamine to cocaine reinforcement mechanisms, which appears to be different to that of the NACC. Moreover, they suggest that FR and PR schedules may measure different aspects of cocaine's CNS action which support self-administration behaviour.

Amygdala↗
PubMed1993

Antagonism of cocaine self-administration by the preferential dopamine autoreceptor antagonist, (+)-AJ 76.

(+)-AJ 76 is a presumed preferential dopamine (DA) autoreceptor antagonist which, in previous behavioral investigations, has displayed properties characteristic of both DA agonists and DA antagonists. In an attempt to test the hypothesis that (+)-AJ 76 might be an effective cocaine pharmacotherapy, the present experiments evaluated (+)-AJ 76's behavioral profile in 3 standard reinforcement paradigms. In the first experiment, (+)-AJ 76 paralleled a DA antagonist in that it failed to support self-administration behavior at all doses (0.1, 0.32, and 1.0 mg/kg/inj) tested. In the second experiment, (+)-AJ 76 (0.9, 3.5, and 14.0 mg/kg) closely resembled the DA agonist D-amphetamine (0.25, 1.0, and 4.0 mg/kg) in producing a clear dose-dependent conditioned place preference. In the third experiment, (+)-AJ 76 (1.88, 3.75, 7.5, 15.0, and 30.0 mg/kg) significantly reduced breaking points (BPs), increased rates of responding, and delayed the onset of responding for cocaine. While (+)-AJ 76 mimics a typical DA antagonist in its ability to reduce BPs and augment rates of responding for cocaine, recent evidence suggests that it more closely resembles a DA agonist in its ability to delay the onset of responding for cocaine. In summary, the present investigations have shown that (+)-AJ 76's profile in 3 reinforcement paradigms is unusual and not exclusively representative of either DA agonists or DA antagonists. The potential utility for such an agent in treating cocaine abuse is discussed.

Animals↗
PubMed1993

Self-administration of GBR 12909 on a fixed ratio and progressive ratio schedule in rats.

Intravenous self-administration of GBR 12909, an indirect dopamine agonist, was examined on a Fixed Ratio (FR 1) and a Progressive Ratio (PR) schedule of reinforcement in rats. Subjects were first trained to self-administer cocaine (1.5 mg/kg/inj) during daily 5 h sessions, after which GBR 12909 (0.187-1.5 mg/kg/inj) was substituted. On the FR 1 schedule, the inter-infusion interval for GBR 12909 self-administration was directly related to dose and was approximately three times longer than that established for equivalent doses of cocaine. Breaking points on the PR schedule were comparable for GBR 12909 and cocaine self-administration. The data indicate that, compared to cocaine, GBR 12909 has a longer duration of action and a similar reinforcing efficacy.

Animals↗
PubMed1993

Heroin self-administration in rats under a progressive ratio schedule of reinforcement.

Heroin self-administration behavior under a progressive ratio (PR) schedule of reinforcement was evaluated in rats. The schedule was designed to restrict drug intake, minimize opiate dependency, and quantify the number of responses emitted (final response ratio) in order to receive a limited number of heroin infusions. Final ratios were found to be stable and did not increase with chronic (31 days) PR reinforcement. The ability of the PR schedule to detect changes in heroin reinforcement was demonstrated by evaluating the effect of naltrexone pretreatment and unit dose alteration on final ratios. Naltrexone (0.4 mg/kg) reduced final ratios and an inverted U dose-response relationship was established for the unit heroin doses 12.5-100 micrograms/injection. Maximal final ratios occurred with 50 micrograms/injection heroin reinforcement. This PR schedule may provide a useful method for evaluating the effects of pharmacological manipulations or lesions on opiate reinforcement.

Animals↗
PubMed1993

L-tryptophan decreases the breaking point under a progressive ratio schedule of intravenous cocaine reinforcement in the rat.

L-Tryptophan (100 mg/kg, IP), the serotonin [5-hydroxytryptamine (5-HT)] amino acid precursor, significantly reduced the mean breaking point maintained under a self-administration progressive ratio schedule of IV cocaine reinforcement (0.6 mg/injection). This effect was produced over the 5 days of self-administration following treatment. Responding maintained under the same progressive ratio schedule for food reinforcement was not affected by L-tryptophan (100 mg/kg, IP). Rats administered L-tryptophan (100 mg/kg, IP) and denied access to cocaine on the day of treatment resumed normal self-administration patterns under a progressive ratio schedule on following test days. This indicates that L-tryptophan treatment alone did not induce long-term effects on cocaine self-administration. Thus, it would appear that the combination of this 5-HT manipulation and cocaine administration altered the reinforcing efficacy of the drug and induced a long-term decrement in breaking point under a progressive ratio schedule. This may have been due to an associative aversion to cocaine self-administration behaviour learned on the day of treatment and carried over to the subsequent 5 days of self-administration access.

Animals↗
PubMed1993

Evaluation of response perseveration of rats in the radial arm maze following reinforcing and nonreinforcing drugs.

The behavioral effects of three drugs with high abuse potential (amphetamine, heroin, and nicotine) and two substances with low abuse potential (haloperidol and scopolamine) were evaluated in an eight-arm radial maze. Rats were trained to explore the maze for the food reward. Unlike most radial arm maze paradigms, a food pellet was made available every time the rat entered an arm; thus, no external restrictions were placed upon rats' exploratory pattern. Following 3 days of drug-free training, rats were injected prior to testing with one of the five drugs. Analysis of the sequences of arm entries demonstrated that the variability of the search strategy was significantly decreased by amphetamine, heroin, and nicotine. In contrast, scopolamine and haloperidol either decreased or had no effect on preservation. These data, along with previous data on ethanol and diazepam, lead to the speculation that drugs of abuse may share the common property of reducing behavioral variability.

Amphetamine↗
PubMed1993

MDL 72222, ketanserin, and methysergide pretreatments fail to alter breaking points on a progressive ratio schedule reinforced by intravenous cocaine.

The effects of three serotonin [5-hydroxytryptamine (5-HT)] receptor antagonists on cocaine self-administration behavior were investigated. Specifically, the effects of MDL 72222 (a specific 5-HT3 receptor antagonist), ketanserin (a specific 5HT2 receptor antagonist), and methysergide (an aselective 5-HT1/5-HT2 receptor antagonist) on the breaking points reached by rats on a progressive ratio schedule for cocaine reinforcement were examined. Pretreatments with MDL 72222 (7.5-1,920 micrograms/kg, SC), ketanserin (0.4-6.4 mg/kg, IP), and methysergide (2.5-20 mg/kg, IP) failed to alter breaking points from baseline values. Although tested at twice the highest doses previously reported to have significant behavioral effects, the three 5-HT receptor antagonists were without effect. These data suggest that relatively specific blockade of 5-HT receptor subtypes does not influence the reinforcing effects of cocaine.

Animals↗
PubMed1993

The effects of dose and access restrictions on the periodicity of cocaine self-administration in the rat.

Cocaine self-administration in rats was tested under various dose and frequency of access restrictions. In the continuous access condition, groups of rats were given continuous, unlimited access to one of three doses of cocaine (1.5, 0.5, and 0.2 mg/kg/infusion) for a duration of 10 days. In the discrete trials condition, a group of rats were given the opportunity to self-administer a single cocaine infusion (1.5 mg/kg) within a discrete, 10 min access trial. The rats received a continuous series of these trials for a duration of 7-10 days at one of three frequencies (1, 2 or 4 trials/h). Results suggest that when access is restricted to four access trials/h, or to a median dose range (0.5 mg/kg per infusion), rats will self-administer cocaine in a cyclical manner over extended, infradian periodicities without developing outward signs of ill health. This contrasts with previous studies where extended, unlimited access schedules have resulted in toxicity and overdose. It is suggested that dose and frequency of access restrictions may be employed in order to develop new animal models of cocaine self-administration which examine the factors underlying the reinitiation of extended periods of cocaine intake. Such models may be useful in testing interventions with the potential to disrupt cyclical patterns of cocaine self-administration.

Animals↗
PubMed1993

Cocaine self-administration increases preprodynorphin, but not c-fos, mRNA in rat striatum.

The impact of cocaine self-administration on the expression of striatal preprodynorphin and c-fos mRNA was examined with in situ hybridization histochemistry. Cocaine significantly increased preprodynorphin mRNA in the dorsal, but not ventral, striatum. Expression of c-fos mRNA in cocaine-administering rats did not differ from that in controls in all structures examined. These results indicate that the expression of preprodynorphin, but not c-fos, is upregulated in rat striatum as a consequence of cocaine self-administration. Furthermore, these data indicate that the regulation of preprodynorphin is dissociable from the expression of c-fos in rats exposed to repeated doses of cocaine.

Animals↗
PubMed1992

Clozapine increases breaking points on a progressive-ratio schedule reinforced by intravenous cocaine.

The effect of the atypical neuroleptic clozapine on cocaine self-administration reinforced on a progressive-ratio schedule in rats was examined. The rat's first response on a lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each infusion until the frequency of responding on the lever fell below a criterion level. The final ratio completed was defined as the breaking point. Doses of 5 and 20 mg/kg clozapine produced either no effect or a nonspecific disruption in responding. Rats pretreated with 10 mg/kg clozapine responded to significantly higher breaking points, indicating an increased motivation to self-administer cocaine.

Animals↗
PubMed1991

Fish and fish oil intake: effect on haematological variables related to cardiovascular disease.

To investigate the effects of practical amounts of n-3 highly-unsaturated fatty acids (HUFA) on a number of parameters involved in haemostasis, 12 healthy men were fed three diets in a 3 x 3 cross-over design. The diets, fed as the evening meal for 6-week periods, were: Control diet (essentially fish-free), Fish diet (200 g/d of lean Australian fish flesh) and the same fish-based diet but supplemented with 5 g/d fish oil (Fish + Oil). The diets supplied about 0, 0.6, and 2.0 g n-3 HUFA/d, respectively. Relative to the Control diet, the number of circulating leukocytes was significantly reduced after both the Fish and Fish + Oil diets (by 13% and 15%, respectively). This reduction occurred in the number of neutrophils, although this did not reach significance on the Fish diet alone. Platelet count fell on the Fish + Oil diet (by 6%) but not on the Fish diet alone. There was an apparent enhancement of fibrinolytic potential after both fish-containing diets, which tended to be accentuated with the fish oil supplementation. The mechanisms underlying some if not all of these observations may be eicosanoid-mediated as indicated by a diminution in the platelet arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios after the Fish + Oil (13.7 +/- 1.8) and Fish (34.4 +/- 8.9) diets relative to the Control diet (66.1 +/- 15.6). These data suggest that a practical amount of lean fish can improve certain haematological parameters implicated in the etiology of cardiovascular disease.

Animals↗
PubMed1991

Fluoxetine pretreatment reduces breaking points on a progressive ratio schedule reinforced by intravenous cocaine self-administration in the rat.

Fluoxetine, a specific serotonin re-uptake inhibitor, reduced the breaking points reached by rats on a progressive ratio (PR) schedule reinforced by intravenous cocaine (0.6 mg/inj). This effect was dose-dependent. Specifically, fluoxetine (2.5, 5.0, 10.0, and 20.0 mg/kg, IP) significantly decreased breaking points at all but the lowest dose. These data support a role for the serotonergic system in cocaine reinforcement. We argue that facilitating serotonergic activity reduces the rewarding value of cocaine, thus suggesting an aversive role for serotonin in cocaine reinforcement.

Animals↗
PubMed1991

3,4-Methylenedioxyamphetamine (MDA) self-administration and neurotoxicity.

3,4-Methylendioxyamphetamine (MDA), a drug with both stimulant- and hallucinogen-like properties, has been used for both medical and recreational purposes. The present study examined the reinforcing effects of MDA in rats and evaluated the resulting neurotoxicity. Self-administration of various doses (0.10, 0.05 and 0.025 mg/injection) was examined on a Fixed Ratio 1 (FR1) and a Progressive Ratio (PR) schedule. MDA supported self-administration at all doses on the FR1 schedule, but overdoses and deaths occurred at the 0.10 mg/injection dose. The breakpoints established on the PR schedule were relatively low. High performance liquid chromatography analyses of the cortex, hippocampus, striatum and nucleus accumbens subsequent to MDA self-administration revealed significant depletion of 5-HT in the hippocampus. The results suggest that MDA is moderately reinforcing and that self-administration of low doses of MDA over several days is selectively neurotoxic.

3,4-Methylenedioxyamphetamine↗