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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of taurine on the analgesic response to morphine, on the intensity of tolerance and on physical dependence were examined. Taurine induced a hyperalgesic state and attenuated morphine analgesia in mice. The hyperalgesia was maximal at a dose level of 1.5 mg/kg i.p., while the effects of higher doses (6.0 and 10.0 mg/kg) were masked by a depression of the animals' gross behavior. Taurine induced a dose related antagonism of morphine tolerance. The amino acid administered 30 min before naloxone, produced a partial reduction in the abstinence signs in the chronically treated mice. Taurine also attenuated the abstinence behavior when administered during the course of dependence. The results are consistent with taurine antagonism to the known effects of morphine on intracellular calcium disposition in nervous tissue.
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PMID:Effects of taurine on tolerance to and dependence on morphine in mice. 653 78

To initiate studies of benzodiazepine tolerance and physical dependence, a reproducible animal model has been developed utilizing chlordiazepoxide in rats. Based on the "chronically equivalent" dosing principle, a regimen has been devised to maintain rats in a state of quantifiable intoxication for 5 weeks. Chlordiazepoxide was delivered intragastrically on a b.i.d. basis in doses individually adjusted day-to-day and animal-to-animal to produce an equivalent impairment of motor function evaluated by a gross neurological screen. Quantitative analysis of central nervous system depression ratings during the time of peak effect (4 hr postdose) confirmed that the criterion of chronic equivalence was indeed met. Over the 5-week period of repeated dosing, tolerance was reflected in a 5-fold increase in maintenance dose, from 163.3 mg/kg on day 2 to 839.3 mg/kg on day 35. Tolerance developed more rapidly during the first 9 to 10 days, but continued to develop thereafter more slowly without apparent ceiling. Upon abrupt withdrawal, a syndrome of hyperexcitation developed. Signs included twitches, tremors, muscle hypertonus, arched back, piloerection, myoclonic jerks, augmented struggle and vocalization upon handling, increased startle response, tail erection, teeth chatter, blanched ears and weight loss. No spontaneous convulsions occurred. Latency to onset of withdrawal ranged from 2 to 5 days, and signs peaked in intensity in 8 days and disappeared by 14 days posttreatment. This animal model appears to provide a useful tool for the study of specific mechanisms underlying benzodiazepine tolerance and physical dependence.
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PMID:Experimental induction of benzodiazepine tolerance and physical dependence. 668 12

Many studies have suggested the importance of the rate of drug elimination in the development of pharmacodynamic tolerance and physical dependence to sedative-hypnotics. However, these studies usually compared drugs whose pharmacokinetic properties differed widely, e.g., short- vs. long-acting barbiturates. Accordingly, we investigated the relationship between individual variations in the rate of elimination of a single drug, pentobarbital, and the severity of physical dependence which developed during chronic pentobarbital administration. Animals were treated with Na pentobarbital according to the "maximally tolerable" dosing schedule described previously, twice a day for 35 days, and abruptly withdrawn. The relationship between chronic treatment variables (doses and blood concentrations of pentobarbital, peak and residual central nervous system depression scores), elimination half-lives and withdrawal intensity were explored. Withdrawal intensity was evaluated as overall withdrawal intensity ratings, the number and types of spontaneous withdrawal convulsions and lethality. Individual variations in the drug elimination half-lives related significantly to the severity of physical dependence produced by pentobarbital: the longer half-life, the more intense the production of physical dependence by pentobarbital.
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PMID:Effects of individual variations in drug elimination kinetics for production of pentobarbital physical dependence. 668 13

A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm. Sodium phenobarbital was administered orally twice daily for 35 days in individually adjusted doses to achieve mean daily peak CNS depression culminating in severe ataxia. Dose to dose continuity of CNS depression was maintained throughout treatment. At the time of dosing rats were mildly ataxic. Following abrupt termination of chronic treatment, an abstinence syndrome characterized by CNS hyperexcitability was observed, which demonstrates physical dependence. Signs, which included motor, autonomic, and behavioral manifestations, appeared from 12-24 h and animals recovered by 12 days. Although tolerance development was nearly complete on day 10 of treatment, the abstinence syndrome observed was more severe following 35 than after 10 days of chronic treatment. Characteristics of tolerance and physical dependence are similar to those described for other species including humans.
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PMID:Phenobarbital tolerance and physical dependence: chronically equivalent dosing model. 668 22

Brain 5-hydroxytryptamine (5-HT) was depleted in rats by intraventricular injection with 5,7-dihyroxytryptamine (5,7-DHT) prior to feeding rats a liquid diet containing ethanol. After withdrawal of ethanol, withdrawal reactions were significantly less severe in 5-HT-depleted rats than control rats. Sleeping times after a standard dose of ethanol or pentobarbitone were significantly prolonged in 5-HT-depleted rats. However, metabolic and pharmacodynamic tolerance developed to a similar extent in 5-HT-depleted rats as in control rats. It was concluded that 5-hydroxytryptaminergic neurons are not directly involved in the development of physical dependence on or tolerance to ethanol. Depletion of brain 5-HT by 5,7-DHT appears to result in a non-specific central nervous system depression that potentiates the depressant actions of ethanol and pentobarbitone and antagonises the hyperexcitability of ethanol withdrawal.
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PMID:Effect of depletion of brain 5-hydroxytryptamine by 5,7-dihydroxytryptamine on ethanol tolerance and dependence in the rat. 676 80

Acute ethanol administration increased methionine-enkephalin (met-enkephalin) and beta-endorphin levels in distinct areas of the rat brain, whereas chronically supplied ethanol caused a depression of met-enkephalin and beta-endorphin levels in most of the brain areas investigated. The beta-endorphin content of the intermediate/posterior lobe of the pituitary of rats and guinea pigs decreased by 70%. Withdrawal of ethanol resulted in a complete recovery of endorphin levels in brain and pituitary within two weeks. Whether the observed alterations in endorphin concentrations are causally related to the primary mechanisms underlying alcohol dependence is uncertain, since no obvious signs of physical dependence were observed in treated animals.
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PMID:Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. 677 6

l-1, 4-Dimethyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine hydrobomide (l-ST-2121) is a new narcotic-antagonist analgesic possessing remarkable analgesic activity, and this activity is equal to or more potent than that of pentazocine. A single administration of l-ST-2121 produced a moderate CNS depression in rats, such as sedation, systemic muscle relaxation and decrease in motor activity. Rats were intermittently mediated for 1 to 6 days at one hour intervals through an implanted intravenous cannula. In a physical dependence producing test, physical dependence on morphine was developed rapidly in the rats maintained with as low as 9.6 mg/kg/day. Physical dependence on pentazocine and l-ST-2121 was also developed with the maintenance dose of 96 mg/kg/day, but not with 9.6 mg/kg/day. However, physical dependence on pentazocine was developed with the maintenance dose of 19.2 mg/kg/day, but l-ST-2121 was not. In a naloxone-precipitated withdrawal test, rats treated with l-ST-2121 (24 mg/kg/day, 48 mg/kg/day and 96 mg/kg/day) showed withdrawal signs when they were given naloxone. Rats treated with morphine or pentazocine also showed withdrawal signs after naloxone challenge. In a substitution test, l-ST-2121 suppressed the withdrawal signs of morphine- and pentazocine-dependent rats, and pentazocine suppressed those of morphine-dependent rats. l-ST-2121 has physical dependence liability of morphine type. The results show that all three drugs induce physical dependence in the order of severity of morphine greater than pentazocine greater than or equal to l-ST-2121.
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PMID:[Physical dependence liability test of l-1, 4-dimethyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine hydrobromide (l-ST-2121) in rats (author's transl)]. 719 46

Male ICR mice (25 - 30 g) were pretreated with bovine hematin (20, 40 or 50 mumoles per kg per day, i.p.) for three days. During the next six-day period, animals received either 50 mg per kg per day propoxyphene-HCl or saline, p.o., in addition to the daily hematin injections. Only the highest hematin regimen depressed the induction of propoxyphene-N-demethylase activity significantly in the drug-treated animals. A similar depression below control levels was noted in the animals receiving only saline (p.o.) and hematin (i.p.). While hematin treatment abolished the metabolic tolerance to propoxyphene analgesia such treatment failed to generate any appreciable degree of physical dependence to propoxyphene as assessed by a challenge with naloxone. These findings may be helpful in assessing the risk factors associated with the widespread use of propoxyphene.
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PMID:The effect of hematin on the development of microsomal enzyme induction and physical dependence in mice following repeated oral propoxyphene administration. 719 21

The physical dependence and tolerance characteristics of barbiturates and ethanol were compared. One group of cats was given anesthetic doses of pentobarbital chronically to produce severe physical dependence ("high dose" group). Two other groups of animals were given barbital or ethanol at "chronically equivalent" doses which produced gross ataxia without anesthesia ("low dose" groups). The doses required to produce the preset level of central nervous system depression progressively increased in all three groups during the chronic administration. Functional tolerance estimated by measuring the drug concentration in the blood at the peak of the drug response was demonstrated in all three groups. Drug administration was terminated after various durations and withdrawal was rated. Severity of withdrawal was assessed by monitoring spontaneous convulsions and by rating motor, autonomic and behavioral signs. These ratings were used to compute peak intensity of withdrawal. The number of convulsions, incidence of lethality during withdrawal and peak withdrawal intensity ratings were considerably higher in the ethanol groups than in the low dose barbiturate groups. Similarly, the number of convulsions, incidence of lethality during withdrawal and peak intensity ratings were consistently higher in the high dose barbiturate groups than in the low dose barbiturate groups. The results indicate that ethanol produced more severe withdrawal than barbiturate when the level of chronic intoxication was comparable in the two groups. Also, the level of central nervous system depression during administration was an important factor influencing intensity of barbiturate withdrawal.
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PMID:Comparison of ethanol and barbiturate physical dependence. 719 50

The experimental results on tolerance to and dependence on phenobarbital (PhB) in male, ICR mice were compared with results previously reported in the case of rats. When food admixed with 1 and 2 mg PhB/g food was administered daily for 13 consecutive days, the mice began to acquire tolerance to PhB from the 4th day or so (rotarod performance test), with little suppression being observed on days 6 or 7. These results indicate that tolerance to PhB is acquired earlier in mice than in rats. The blood and brain concentrations of PhB during the dosing period were reduced abruptly on the 3rd or 4th day, corresponding well with the time course changes in the development of tolerance shown by rotarod performance. The mice were given daily doses of PhB increasing stepwise from 0.5 and 1 mg PhB/g food to 4 mg PhB/g food, over 39 consecutive days. With this gradually increasing dose regimen, the animals maintained moderate to severe depression of CNS throughout the dosing period. The blood and brain half-life of PhB after withdrawal were 16 and 8 hr respectively. From 17 to 24 hours after withdrawal of PhB, the animals showed signs of systemic tremors, Straub-tail, hyperkinesia, wild running "rum fits" and clonic-tonic convulsions. Contrary to the findings in rats, in which there was a frequent incidence of convulsion from 17 to 48 hours after withdrawal, the duration of the characteristic signs after barbiturate withdrawal was obviously short-term. These results suggest that may be more reasonable to use rats in preference to mice as a preclinical model of dependence, especially in cross-physical dependence tests for sedative-hypnotic drugs.
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PMID:Tolerance to and dependence on barbiturates in mice reference to the data in rats. 719 64


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