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Biomedical subjects

G Prat

Publications and source records attributed to G Prat.

At least 19 recordsLinked to original sources

Reliability of the Spanish version of the Composite Scale of Morningness.

AIM: The aim of this study was to examine the reliability of the Spanish version of Composite Scale of Morningness (CSM) and its ability to measure the circadian typology. SUBJECTS AND METHODS: Voluntary and unpaid psychology students (N= 391; 132 men and 259 women), aged between 17 and 33, completed the questionnaire between the months of September and December. RESULTS: The total score was independent of age and gender, with a close to normal distribution and a non-significant negative skewness. The internal consistency was high (Cronbach's alpha= 0.87) and factor analysis extracted three factors labeled Time of Retiring (items 2 and 7), Activity Planning (items 8, 9, and 13) and Morning Affect (items 3-6, and 10-12). With the 10th and 90th percentiles as cut-off scores, scorers below 22 (N= 40; 10.2%) are classified as evening-types and scorers above 39 as morning-types (N= 28; 7.2%). CONCLUSION: The Spanish questionnaire shares most of the good psychometric properties of other versions of the CSM, and thus can be used for Spanish-speaking student samples. Nevertheless, further studies of normative data in workers and aged subjects are needed in order to validate CSM.

Adolescent↗

Effects of sub-chronic combined treatment with pergolide and caffeine on contralateral rotational behavior in unilateral 6-hydroxydopamine-denervated rats.

We studied the synergistic effects of pergolide and bromocriptine with caffeine on turning behavior in 6-OHDA denervated rats. Both pergolide and bromocriptine were synergistic with caffeine, and prevented tolerance to caffeine-induced turning. When caffeine was removed, tolerance to bromocriptine effects was observed for 1 day only, while no tolerance was observed to pergolide. These results suggest that caffeine could be useful in the treatment of Parkinson's disease, preferentially as an adjuvant of mixed dopaminergic agonists like pergolide.

Animals↗

Lack of synergism between caffeine and SKF 38393 on rotational behavior in 6-hydroxydopamine-denervated rats.

We have recently shown a synergistic effect between caffeine and the dopamine D(2) receptor agonist, bromocriptine, on contralateral rotational behavior in unilaterally 6-hydroxydopamine-denervated rats. In addition, we found that bromocriptine prevented caffeine-induced tolerance to this behavior following repeated treatment. In the present study, we investigated whether or not the dopamine D(1) receptor agonist, (+/-)-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393), presented similar characteristics. Different groups of rats received simultaneous injections of either vehicle plus vehicle, caffeine (40 mg/kg) plus vehicle, SKF 38393 (0.5, 1, 2, and 4 mg/kg) plus vehicle, or caffeine plus SKF 38393 (0.5, 1, 2, and 4 mg/kg) for 5 consecutive days, and both ipsilateral and contralateral rotational behavior was measured. Results showed that, on the first day of treatment, caffeine produced significantly more rotational behavior than did a low dose of SKF 38393 (0.5 mg/kg), and significantly less turning than at higher doses (2 and 4 mg/kg). Combined treatment with caffeine and a high dose of SKF 38393 (4 mg/kg) produced significantly more rotational behavior than did caffeine plus vehicle. With repeated administration, caffeine produced sustained tolerance to its effects on rotational behavior, whereas SKF 38393 did not. In the groups treated with low doses of SKF 38393 (0.5, and 1 mg/kg) plus caffeine, tolerance was observed while in the groups that received high doses of SKF 38393 (2 and 4 mg/kg) plus caffeine, no tolerance was observed to rotational behavior. These results suggest that maximal stimulation of dopamine D(1) receptors may be needed to prevent the tolerance effects of caffeine in this animal model. This finding may have clinical relevance to the therapeutic treatment of Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned rats.

The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60mg/kg) were administered 30 min before an injection of L-DOPA (25mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20mg/kg), the MAO A inhibitor, clorgyline (20mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose-related manner. At the dose of 40 and 60mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease.

Adrenergic Agents↗

Methylxanthines reverse the adipsic and aphagic syndrome induced by bilateral 6-hydroxydopamine lesions of the nigrostriatal pathway in rats.

This study investigated whether methylxanthines (caffeine and theophylline) would restore food and water intake in rats made aphagic and adipsic by bilateral 6-hydroxydopamine lesions of the nigrostriatal bundle, and these results were compared with the effects of d-amphetamine, the dopamine D(1) agonist SKF 38393, and the D(2/3) agonist quinpirole. In a separate experiment, we investigated whether the selective D(1) antagonist, SCH 23390, or the selective D(2) antagonist, sulpiride, would prevent the caffeine-induced restoration of food and water intake in bilaterally 6-hydroxydopamine denervated rats. The results showed that caffeine, theophylline, and quinpirole significantly reversed the aphagia and adipsia observed in lesioned animals. SKF 38393 had no significant effects on water intake, while it significantly restored food intake at the highest dose used. In contrast, d-amphetamine had no significant effects on food or water intake. Results from the second experiment showed that sulpiride attenuated the caffeine-induced restoration of food and water intake in lesioned rats to a greater extent than did SCH 23390. These data suggest that methylxanthines may mediate their effects on food and water intake in bilateral 6-hydroxydopamine-lesioned rats through an action at the dopaminergic system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Striatal dopaminergic D(2) receptor density measured by [(123)I]iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients.

OBJECTIVE: The authors' goal was to study striatal dopaminergic dopamine 2 (D(2)) receptors as a biological marker of early relapse in detoxified alcoholic patients by using [(123)I]iodobenzamide ([123I]IBZM) single photon emission computed tomography (SPECT). METHOD: The authors performed [(123)I]IBZM SPECT on 21 alcohol-dependent inpatients during detoxification and on nine healthy volunteers, using the ratios of basal ganglia to occipital lobes for SPECT quantification. Depending on treatment outcome 3 months after hospital discharge, patients were determined to be relapsers or nonrelapsers. RESULTS: Alcohol-dependent subjects with early relapse (within 3 months after hospital discharge) showed a higher uptake of [(123)I]IBZM in the basal ganglia during detoxification (mean ratio=1.83, SD=0.9) than patients who did not have early relapse (mean ratio=1.69, SD=0.11). CONCLUSIONS: These results suggest that low levels of dopamine, or an increased density of free striatal dopaminergic D(2) receptors, could be related to early relapse in alcohol-dependent patients. Therefore, [(123)I]IBZM SPECT could become a biological marker of vulnerability to relapse for alcoholic patients in recovery.

Adult↗

Scopolamine prevents tolerance to the effects of caffeine on rotational behavior in 6-hydroxydopamine-denervated rats.

Continuous administration of caffeine has been shown to induce tolerance to its psychostimulant effects. In this study, using unilateral 6-hydroxydopamine nigrostriatal denervated rats, we tested the hypothesis that the muscarinic receptor antagonist, scopolamine, would prevent the tolerance to caffeine-induced contralateral rotational behavior. For that purpose we administered either caffeine (40 mg/kg) plus saline or scopolamine (5, 10 and 20 mg/kg) plus saline, as well as caffeine in combination with the various doses of scopolamine for 7 consecutive days, and measured ipsilateral and contralateral rotational behavior. The results showed that acute injections of scopolamine plus saline produced similar levels of both ipsilateral and contralateral turning, while caffeine produced more contralateral than ipsilateral turning. Tolerance to caffeine-induced contralateral turning was observed as of the second administration, while scopolamine plus saline injections did not produce significant changes in rotational behavior with repeated treatment. Scopolamine co-administered with caffeine significantly attenuated the increased contralateral turning produced by acute injections of caffeine plus saline, but significantly prevented the tolerance effects with repeated administration. These findings strongly suggest that muscarinic cholinergic processes may be involved in tolerance to caffeine-induced contralateral turning. The results are interpreted in terms of the possible interactions between dopamine, adenosine and acetylcholine neurotransmitter systems within the basal ganglia circuitry involved in motor behavior.

Animals↗

Rotational behavior in dopamine nigrostriatal denervated rats: effects of a wide range of time intervals between apomorphine administrations.

Previous studies using the turning behavior animal model have shown both increases and decreases in rotational behavior following successive administrations of dopamine agonists. To clarify the results obtained with this model, we studied the variability of rotational behavior after repeated challenges with low doses of apomorphine (0.05 mg/kg) at different time intervals ranging between 2 h and 14 days. Results show a decrease in the total number of turns with time intervals of 2, 6, and 12 h between administrations, and an increase in the total number of turns when apomorphine was administered once every 24 h. In contrast, when animals were tested at 7- and 14-day intervals, a stable number of turns in successive challenges was obtained. These results suggest that when successive injections of dopamine agonists are administered at sufficiently long intervals of time, the neuroadaptations that take place due to repeated drug exposure may not be apparent. These findings are relevant for the design of future experiments using this model.

Animals↗

Repeated co-administration of caffeine and bromocriptine prevents tolerance to the effects of caffeine in the turning behavior animal model.

The present study examined the effects of repeated co-administrations of caffeine and bromocriptine for 9 consecutive days on contralateral turning in unilateral nigrostriatal 6-hydroxydopamine denervated rats. In agreement with previous data, our results showed that on the first administration, both caffeine and bromocriptine injected plus saline produced a significant increase in contralateral rotational behavior as compared to saline-saline injections. However, with repeated administrations, tolerance was observed to caffeine, but not to bromocriptine. The combination of different doses of bromocriptine (0.1, 0.2, 0.4 and 0.8 mg/kg) with caffeine (40 mg/kg) significantly enhanced the effects of either drug injected with saline on rotational behavior, and no tolerance was observed with repeated treatment. The continuous co-administration of both substances was necessary to maintain elevated levels of rotational behavior, since withdrawing one or the other drug led to decreased contralateral turning. These results demonstrate that when caffeine is administered repeatedly in combination with bromocriptine, tolerance to its psychostimulant effects is not observed, suggesting that caffeine could be used as an adjunctive therapeutic agent with dopamine agonists for the treatment of Parkinson's disease.

Adrenergic Agents↗

Effects of bromocriptine on self-administration of sweetened ethanol solutions in rats.

The effect of bromocriptine (BRO), a D2 receptor agonist, on chronic oral ethanol (ETOH) self-administration was tested in a home-cage environment. Male Wistar rats (n = 77) were food deprived for 24 h. Then, a period of 15 days of limited-access (1 h/day) to food and to a sweetened ETOH solution was started [3% w/v of glucose and several concentrations of ETOH depending upon the group: 0% (control group). 1.5%, 5% or 10% v/v]. Later, another period started in which rats were maintained in a free-choice, two-bottle situation with food, tap-water and the sweetened solution available for 24 h/day, for 14 days. Following this period, BRO (5 mg/kg, SC) was administered, once daily, for 5 days, in the same continuous free-access conditions. ETOH consumption was also studied for 4 days after the last BRO injection. BRO increased ETOH self-administration throughout the 5-day period, regardless of the ETOH concentration available, in the rats with previous higher ETOH intake, without effect in the control animals. In the control rats, water intake was increased, whereas in the group that had access to the lowest ETOH concentration a decrease in water consumption was found. The enhanced ETOH drinking was maintained after BRO treatment for the animals with previous higher ETOH intake. BRO effects on water consumption were also maintained. These data suggest that BRO can potentiate ETOH intake and provide further support for the role of dopamine (DA) systems in mediating volitional oral intake of ETOH.

Animals↗

The apomorphine test in heroin addicts.

Chronic administration of opiates to laboratory animals induces supersensitivity of the dopamine receptors in the cerebral areas innervated by the mesotelencephalic dopamine pathways. In humans, the in vivo study of the sensitivity of the dopamine neurotransmitter system in Parkinson's patients can be done by means of the apomorphine test, which consists of measuring the number of yawns induced by the subcutaneous administration of low doses of apomorphine (0.005 mg/kg). If chronic opiate use in humans, as in experimental animals, results in supersensitivity of the dopamine systems, the apomorphine test could differentiate between heroin addicts and healthy volunteers, with the former showing greater number of yawns. In order to test this hypothesis we carried out the apomorphine test in two groups of subjects: a group of male heroin addicts attending our Addiction Treatment Centre for detoxification and the other group consisting of healthy volunteer male university students. Results showed that subcutaneous apomorphine administration induced a greater number of yawns (p < 0.05) in the group of heroin addicts as compared with the group of healthy volunteers, suggesting that heroin addicts present an enhanced sensitivity of the dopamine nuerotransmitter system.

Adolescent↗

[Sublingual captopril versus nifedipine in the treatment of hypertensive crisis].

The currently accepted drug of choice for treatment of hypertensive crisis is sublingual nifedipine. We compared the effects of sublingual captopril (25 mg) to those of nifedipine (10 mg) in 54 patients with this complication who came to the emergency room. Five min after administration of captopril, blood pressure decreased from 197.5 +/- 32.7/118.3 +/- 8.2 to 156 +/- 27.2/95.8 +/- 12.9 mmHg and heart rate decreased from 87.9 +/- 15.1 to 74.7 +/- 10.9 (p < 0.05). Blood pressure in the nifedipine group decreased from 198 +/- 27.3/120 +/- 9.8 to 147.7 +/- 17.8/86 +/- 17.9 (p < 0.05), while no change was observed in heart rate. Delayed measurements showed lower diastolic pressures at 60 and 75 min and lower systolic pressure at 120 min in the nifedipine group (p < 0.054). Few and not significantly different side effects were observed with both drugs. Thus, sublingual captopril is useful for treatment of hypertensive crisis.

Administration, Sublingual↗

T-maze performance in rats following chronic neuroleptic treatment.

The effects of chronic haloperidol treatment (0.5 mg/kg/day for 21 days) on maze learning in the rat were studied. There were no differences between haloperidol- and saline-treated groups in percentage of correct responses, but the latency to respond was longer and extinction was faster in the haloperidol-treated group. We speculated that differences between both groups were due to a decrease of appetitive motivation in haloperidol-treated animals, probably caused by a decrease of dopaminergic neurotransmission.

Animals↗

Is experimental catalepsy properly measured?

Following logarithmic transformation (ln) of total duration of haloperidol-induced catalepsy in the rat, measured by means of the bar test, a normalization of the results is achieved. With the help of this transformation we have been able to study what are probably the most important variables involved in the measuring of experimental catalepsy and to establish some criteria for a better use of such measures: 1) repeated measures of catalepsy have to be taken in order to avoid the stress-induced inhibition of catalepsy caused by the new experimental situation, 2) the dose of neuroleptic used has to be sufficiently low to permit the measurement of total or real duration of catalepsy between two determinations, and 3) the dose of neuroleptic has to be sufficiently high to prevent the development of a learned "pseudocatalepsy."

Adrenal Glands↗

Conditioning of rotational behavior after the administration of a single dose of apomorphine in rats with unilateral denervation of the dopaminergic nigrostriatal pathway: relevance to drug addiction.

Our aim is to study the relationship of drug activation of the dopamine neurotransmission system and the conditioning of environmental stimuli present at the time of drug administration. We injected a single dose of apomorphine (0.05 mg/kg SC) in rats with the nigrostriatal dopamine pathways unilaterally denervated with 6-hydroxydopamine, which generates rotational behavior contralateral to the lesioned hemisphere. We observed rotational behavior without apomorphine administration when animals were reexposed at different time intervals to the same environment in which they performed turning behavior. The present findings show that this rotational behavior can be conditioned to environmental stimuli in a strong and long-lasting way. In light of the relationship between opioids and the dopaminergic system, similar conditioning could take place in the learning processes implicated in drug addiction.

Animals↗