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Biomedical subjects

M Babbini

Publications and source records attributed to M Babbini.

At least 37 records · Page 2Linked to original sources
PubMed1990

Multiple-dose pharmacokinetics of naproxen from a controlled-release tablet in healthy volunteers.

The pharmacokinetics of a new controlled-release tablet of naproxen (750 mg) given once daily has been studied in healthy volunteers, in comparison with two doses of the conventional naproxen tablets (375 and 500 mg) administered twice daily. Steady-state plasma concentrations of naproxen were achieved after two days of repeated administration of both the controlled-release and the conventional tablets. On day seven, peak concentration, cowest concentration and the steady-state average plasma concentration values of the controlled-release tablet were significantly higher than those of 375 mg conventional tablet and comparable to those of 500 mg conventional tablet. Areas under the plasma concentration-time curve indicated an equal extent of absorption between the new and the conventional formulation. Overall the controlled-release tablet administered once daily mimicked a twice daily regimen so suggesting that the new formulation could be suitable for once daily dosing.

Adult↗
PubMed1989

Cross-tolerance between morphine and clonidine: a study on motility in rats.

The effects of clonidine on motility were determined in non-dependent, morphine-dependent (a 20 mg/kg dose i.p. for 26 days) and post-dependent rats. In naive animals, clonidine (30-100 micrograms/kg) produced a dose-related suppression of motility. However, when the drug was administered in morphine-dependent rats, it induced slight hyperactivity at small doses and a decrease of activity only at the largest dose (100 micrograms/kg). Thus, tolerance to morphine conferred cross-tolerance to clonidine. On the contrary, the effects of clonidine on motility in post-dependent animals did not differ from those observed in control animals. The results are discussed in terms of similarities and differences between the depressant and excitatory effects of morphine and clonidine.

Animals↗
PubMed1989

Time-dependent generalization of morphine stimulus properties to meperidine: antagonism by naloxone.

The time course of the stimulus generalization to morphine by meperidine (20 mg/kg) was determined in rats trained to discriminate morphine (10 mg/kg) from saline in a standard two-lever procedure with food reinforcement. It was found that morphine lever selection following meperidine was a strictly time-dependent phenomenon. Naloxone (0.3 mg/kg) antagonized the stimulus properties of both morphine and meperidine; however, the antagonism was significantly more pronounced against morphine. The results suggest that there may be certain differences in the neuropharmacology of the stimulus properties of morphine and meperidine.

Animals↗
PubMed1987

Increased sensitivity to the stimulus properties of morphine in food deprived rats.

Recent research has shown that food deprivation increases opiate self-administration; in this line a first purpose of the present experiments was to determine whether the food deprivation effect could be replicated by the use of place conditioning, an alternative procedure for the study of drug reinforcement. It was found that the conditioned reinforcing properties of morphine (2.5 mg/kg IP) paired cues are greater in food deprived rats both after 1 and 3 conditioning sessions. A second objective of the work was to examine the possibility that food deprivation could also influence the discriminative stimulus properties of opiates. To this end rats trained to discriminate 10 mg/kg IP of morphine from saline were submitted to morphine generalization tests when food deprived or after 15 min supplemental feeding in the home cages. The ED50 value was significantly lower for food deprived (6.09 mg/kg) than for partially satiated (7.79 mg/kg) rats. It was concluded that food deprived rats are mores sensitive to both the reinforcing and the discriminative stimulus properties of morphine.

Animals↗
PubMed1986

Sensitivity to the narcotic cue in non-dependent, morphine-dependent and post-dependent rats.

Using a food-reinforced two-lever operant procedure, 12 rats were trained to discriminate 10 mg/kg (i.p.) of morphine from saline. Five animals were given daily non-contingent exposure to morphine (20 mg/kg on saline, or no-test days, and 10 mg/kg on drug days) from the beginning of the experiment; the others received injections of saline. In the morphine generalization tests, the dependent rats showed an increased sensitivity to the narcotic cue as compared with non-dependent animals (ratio of the ED50 values: 2.30). This increased sensitivity was still present 3 months after discontinuing the non-contingent treatment with morphine (ratio of the ED50 values: 1.98). The results of the present study, together with other results reported in the literature, suggest that the experimental procedure plays a role in determining whether tolerance, no tolerance or enhanced sensitivity to the discriminative stimulus properties of narcotics, is observed.

Animals↗
PubMed1985

Cross-sensitization to the excitatory effect of morphine in post-dependent rats.

Time-effects of morphine, methadone, meperidine and pentazocine upon locomotor activity were investigated in naive and in post-dependent rats. Dependence was induced by daily injection of 20 mg/kg (i.p.) of morphine for 30 days. Tests were run starting from 1 month after withdrawal from morphine. Morphine produced a greater increase in activity in post-dependent than in naive rats. Marked cross-sensitization to the excitatory effect occurred with methadone but not with pentazocine. The motility pattern of meperidine was similar in naive and in post-dependent animals. The findings presented here suggest that: different mechanisms underlie the excitatory actions of opiates; the narcotic character of a drug can be detected by challenging this drug in rats previously dependent on morphine.

Animals↗
PubMed1985

Morphine and clonidine oral self-administration: a study in morphine dependent or abstinent rats.

The ability of morphine and of clonidine to support self-administration has been evaluated in morphine dependent or abstinent rats, using an orally reinforced operant technique (F.R. 20). It was found that: Morphine drinking can function as a reinforcer of an operant response both in dependent and abstinent rats. The bitter taste of morphine becomes a secondary reinforcer for rats usually working for the alkaloid. Clonidine supports oral self-administration in morphine abstinent, but not in morphine dependent rats. The data are in line with clinical findings and give a further evidence that oral self administration in rats can be an useful model for the analysis of drug dependence.

Animals↗
PubMed1984

Stimulus properties of clonidine in chronically morphine treated rats trained to a morphine-saline discrimination.

In an operant behavior procedure of lever pressing on an FR 10 schedule of food reinforcement, morphine dependent and nondependent rats were trained to respond on a lever on one side of the food tray after a morphine (10 mg/kg i.p.) injection and to respond on a lever on the alternate side after a saline injection. Following discrimination training, in both dependent and nondependent rats saline was generalized to various doses of clonidine (10, 30 and 50 micrograms/kg i.p.). A response inhibition of about 65% was obtained with the highest dose. It was concluded that, even if clonidine can suppress signs of narcotic withdrawal, the internal state induced by morphine in an abstinent rat does differ from the one induced by clonidine in the same animal.

Animals↗
PubMed1983

Further evidence for a motility substitution test as a tool to detect the narcotic character of new drugs in rats.

Time effects of three doses of codeine, d-propoxyphene, meperidine and dextromethorphan upon locomotor activity have been investigated in naive rats as well as in animals treated chronically with 20 mg/kg of morphine daily. The first three drugs exhibited a motility pattern qualitatively similar to that of morphine; in chronically-treated rats cross-tolerance occurred to acute depressant effects and cross-sensitization to acute excitatory effects. In the case of meperidine however cross-sensitization appeared to be small. Dextromethorphan presented effects similar to morphine only in a very large dose. The present data, together with those of previous work, demonstrate that a locomotor activity substitution test may predict the morphine-like addictive properties of a drug.

Animals↗
PubMed1983

Long-term sensitization to the excitatory effects of morphine. A motility study in post-dependent rats.

Motility effects of excitatory and depressant doses of morphine were studied in naïve, dependent (20 mg/kg daily) and post-dependent (about 40 days after withdrawal) rats. Doses of 0.6 and 1.25 mg/kg of morphine produced a greater increase in activity in post-dependent than in naïve rats. A 20-mg/kg dose exerted an excitatory effect in dependent rats instead of the depressant one induced in naïve animals. This excitatory effect was still evident but less pronounced in post-dependent rats. The dose of 1.25 mg/kg was repeatedly challenged in post-dependent (80 mg/kg daily) rats. It was found that the increased excitatory effect of this dose persisted unchanged 160 days after ceasing treatment. The present results demonstrate that several months after the withdrawal of morphine, sensitization still exists to the excitatory effect of the drug while tolerance to the depressant action is slight or no longer present shortly after ceasing treatment.

Animals↗
PubMed1982

Benzodiazepine effects upon Geller-Seifter conflict test in rats: analysis of individual variability.

The aim of the present study was to investigate in a large group of "drug sophisticated" animals the effect of several doses of oxazepam upon conflict behavior. To this end 43 rats, trained according to the original Geller-Seifter paradigm, were tested with 5 doses (6.25, 12.5, 20.9, 25, and 50 mg/kg IP) of oxazepam. In addition the influence of prior drug experience on the effects of benzodiazepines on punished and unpunished responding was investigated comparing data from the same animals relative to a single oxazepam treatment before and after "drug sophistication." It was found that: (1) after "drug sophistication" oxazepam effect upon the unpunished schedule is decreased, while the disinhibitory action upon punished behavior is increased, unchanged or even decreased; (2) sedative and anticonflict activities of the drug cannot be explained in terms of rate dependency and are independently assessable since, even when unpunished responding is lowered by high doses, the anxiolytic effect is masked in only 27% of the cases; (3) about 20% of the animals appear to be insensitive to the anticonflict effect of oxazepam; (4) the responsiveness to the anxiolytic effect of the drug is related to the shock intensities given during training and to the animal variability under control conditions.

Animals↗
PubMed1980

Morphine effects upon discriminated approach and discriminated avoidance in rats: antagonism by naloxone.

The effects of various doses of morphine (5, 10 and 20 mg/kg) alone or in combination with a constant dose of naloxone (1.25 mg/kg) were examined in rats trained on a discriminated approach schedule (in which bar pressing in the presence of a stimulus light produced food), or on a discriminated avoidance (in which the same response produced stimulus-shock termination). Since the performance of rats in the discriminated avoidance varied widely, drug effects were examined separately in groups of good, intermediate or poor performer rats. Comparable patterns of responding in the presence of light were found in the approach group and in the good performer avoidance group. Morphine induced a dose-related decrease of this responding which was identical in both cases. Other effects of morphine were a dose-related increase of escape failures in all the avoidance groups and stimulatory or depressant effects upon bar presses performed during the no light periods. All the effects of morphine were antagonized by naloxone. The data suggest that comparable patterns of responding maintained by different reinforcements can be similarly affected by morphine.

Animals↗
PubMed1980

Rm values and structure-activity relationship of benzodiazepines.

Quantitative structure-activity relationships (QSAR) have been formulated for the activities of a series of benzodiazepines in rats. The lipophilic character of molecules was expressed by means of the chromatographic Rm values which were very well correlated with experimental or calculated log P values. The ideal lipophilic character for activity of benzodiazepines in the exploratory behavior test is not far from that of compounds acting in the central nervous system as unspecific depressant agents. The results of both the conflict and exploratory behavior studies might support the hypothesis of different sites of action for the antianxiety and sedative effects of benzodiazepines.

Animals↗
PubMed1979

Stimulus-response relationships in a quickly learned escape from shock: effects of morphine.

The relationship between stimulus intensity and analgesic effectiveness of morphine was investigated by means of an operant technique. Various doses of morphine were tested in rats trained to press a bar to escape from shocks of varying intensity. Under control conditions a good linear relationship between the log of the stimulus intensity and the log of the speed to press the lever was found. Morphine showed inhibitory effects upon this escape behavior, which were greater at any given dose with greater intensity of the shock. These effects were dose related, that is, the slopes of the shock-response lines decreased by increasing the dose. The data obtained do not appear to be a consequence of a general depressant effect of the drug upon behavior and are in line with several experimental observations showing that in animals, as well as in humans, the magnitude of the analgesic effect of morphine tends to increase as pain severity increases.

Animals↗