Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The establishment of, and sex differences in, physical dependence on methaqualone (MQ) in rats were studied by the drug-admixed food (DAF) method. Female and male rats were treated with MQ-admixed food on the same schedule of gradually increasing doses (0.5 and 1 to 6 mg of methaqualone/g of food). Only female rats showed hypothermia from MQ at 1 and 2 mg/g and motor incoordination from MQ at 4 and 6 mg/g of food. Moreover, after MQ withdrawal, severe withdrawal signs, including convulsions and death, were observed in female rats, but not in male rats. We also instituted a different schedule of graded increases in dose (1 and 2 to 10 and 12 mg/g of food) to develop physical dependence on MQ in male rats. Under this schedule male rats exhibited a hypothermia and severe motor incoordination from MQ 6 and 8 mg/g of food condition. After MQ withdrawal, various severe signs of MQ withdrawal occurred, including tremor, convulsions and death. These results demonstrate that severe physical dependence on MQ in both sexes can be established using the DAF method, and that there are marked sex differences in the physical dependence on MQ.
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PMID:Sex differences in physical dependence on methaqualone in the rat. 317 79

Sprague-Dawley male rats were intoxicated with morphine, using an ingestion method where exposed and control rats received equivalent amounts of calories and nutrients. The degree of physical dependence on morphine was demonstrated by studying and quantifying abstinence symptoms after withdrawal or after administration of opiate antagonists. The aims of the study were (1) to further enlighten the specificity and validity of the intoxication method concerning physical dependence, and (2) to determine whether some of the abstinence signs might be of value to facilitate quantitation of the degree of physical dependence on morphine, with diet and fluid intake being maintained under control. Withdrawn rats showed a decreased fluid diet intake and a body weight loss, the latter partly due to anorexia. Other mild abstinence signs were irritation, tremor and some motor excitation. The body weight loss during the first day of morphine withdrawal was proportional to the accumulated drug dose (between 25 and 300 mg morphine PO/kg b.wt.). However, prolonged morphine treatment on one dose (340 mg/kg b.wt.) did not reinforce the body weight changes caused by morphine withdrawal. The succeeding weight gain some days after morphine withdrawal was not entirely dependent on the amount of fluid diet intake. Methadone was shown to partially block the decrease in diet intake and the weight loss seen during morphine withdrawal. The naloxone-precipitated withdrawal symptoms were motor excitation, cholinergic signs, body weight loss, diarrhoea and decreased diet intake. The weight loss 2 hr after naloxone administration to long-term intoxicated rats was proportional to the naloxone dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aspects of abstinence after morphine ingestion. 365 10

Twenty generations of selective breeding were used to produce lines (strains) of mice which differ markedly from one another in ethanol physical dependence development as indexed by handling-induced convulsions (HIC) induced by withdrawal from ethanol. These withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines now differ by over 10-fold in HIC scores after equivalent exposure to intoxicating levels of ethanol via inhalation. Since handling-induced convulsions can be readily elicited following withdrawal from nitrous oxide, we sought to determine if the very large differences in ethanol withdrawal-induced HIC bred into these selection lines would generalize to nitrous oxide. Following a 60 min exposure to 75% nitrous oxide (in O2), a greater than 10-fold difference in HIC scores, and a 2-fold difference in tremor incidence was seen upon withdrawal in WSP vs. WSR mice. These findings closely parallel those seen with ethanol, and demonstrate that a large degree of commonality exists in the genes and the mechanisms determining these withdrawal signs. HIC elicited by nitrous oxide withdrawal were readily suppressed by ethanol, and HIC elicited by ethanol withdrawal were promptly suppressed by 75% nitrous oxide in WSP mice. Nitrous oxide also suppressed HIC and tremor associated with nitrous oxide withdrawal.
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PMID:Ethanol and nitrous oxide produce withdrawal-induced convulsions by similar mechanisms in mice. 366 9

In order to elucidate the fundamental differences between alcohol and barbital physical dependence, comparative studies were made on the effect of various drugs on the withdrawal signs developed in alcohol and barbital dependent mice. Ethanol, barbital and diazepam, drugs of alcohol-barbiturate type dependence liability, and ethosuximide, an anticonvulsant, suppressed both withdrawal signs in a dose dependent manner. The effects of these drugs were different from each other only quantitatively and no special difference was observed between the effects on alcohol and barbital withdrawal signs. On the other hand, the effects of phenytoin, an anticonvulsant, and pentylenetetrazol, a convulsant, were only evident in alcohol dependent animals. Phenytoin elicited body tremor and markedly exacerbated the alcohol withdrawal signs, but slightly suppressed the barbital withdrawal signs. Dose-response curves for the convulsive effect of pentylenetetrazol obtained at the peak of the withdrawal signs shifted greatly to the left in alcohol withdrawn animals but less in barbital withdrawn animals. These discrepancies between the effects on alcohol and barbital withdrawal signs may suggest a difference in the underlying mechanisms for the production of alcohol and barbital physical dependence.
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PMID:Differentiation of alcohol and barbital physical dependence. 377 53

Dogs, surgically implanted with a chronic gastric fistula, were chronically dosed with N-desmethyldiazepam (32 mg/kg/day) in four divided doses to attain N-desmethyldiazepam plasma levels comparable to those observed in dogs dependent on diazepam (60 mg/kg/day). The time course of N-desmethyldiazepam abstinence was studied, beginning not less than 2 weeks after stabilization levels had been achieved. The abstinence syndrome observed after abrupt discontinuation of N-desmethyldiazepam was similar to the diazepam abstinence syndrome but differed in several important aspects. In diazepam-dependent dogs, there was a short burst of tremor very early in withdrawal (approximately 1-2 hr after the last dose of diazepam) that was not seen in N-desmethyldiazepam-dependent dogs. Signs of abstinence such as tremor, hot foot walking and twitches and jerks were more frequently observed in N-desmethyldiazepam-dependent dogs than in diazepam-dependent dogs as were decreases in food and water intake and in body weight. The overall intensity of abstinence, as measured by the Diazepam Withdrawal Abstinence Scale, was greater in N-desmethyldiazepam-dependent dogs than in dogs dependent on either lorazepam or diazepam. Plasma levels of N-desmethyldiazepam and oxazepam were nearly equal in dogs dependent on diazepam or on N-desmethyldiazepam and were 4 to 10 times greater than the plasma levels of diazepam or lorazepam in diazepam- or lorazepam-dependent dogs, respectively. Furthermore, the plasma levels of N-desmethyldiazepam and oxazepam declined much more slowly than the levels of diazepam and lorazepam. These results suggest that physical dependence on diazepam is caused by the accumulation and actions of N-desmethyldiazepam.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-desmethyldiazepam physical dependence in dogs. 393 42

Rats chronically implanted with osmotic minipumps in the left lateral ventricle were used to study the ability of dermorphin to produce tolerance and physical dependence. The development of tolerance, assessed by evaluating the time reduction of analgesia, catalepsy and rigidity, occurred in a dose-dependent fashion over a maximum period of 48 h. After 3 days of peptide infusions into the rat brain, the dependent state was established and was revealed by precipitating the withdrawal syndrome with intraperitoneal naloxone injections. Escape behavior, shaking, salivation and rhynorrhea were the main symptoms, qualitatively similar to those obtained in rats made dependent on morphine. Considering that dermorphin displays strong analgesic activity, the well-known combination of antinociception tolerance and dependence capacities of opiates also seems to be valid for dermorphin.
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PMID:Tolerance and physical dependence induced by dermorphin in rats. 404 26

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.
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PMID:Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat. 612 98

Dogs, surgically implanted with a gastric fistula, were chronically dosed with diazepam or lorazepam. Diazepam (60 mg/kg/day) or lorazepam (100 mg/kg/day) was administered intragastrically in four divided daily doses. Beginning no less than 2 weeks after the attainment of stabilization doses, dogs underwent withdrawal experiments, repeated at 2-week intervals. At a time of withdrawal determined by a Latin square crossover design, dogs were observed for 8 hr for signs of abstinence. Both diazepam and lorazepam caused a withdrawal abstinence syndrome to appear upon abrupt discontinuation of the drug. The two abstinence syndromes had many signs in common, including tremor, hot foot walking, rigidity and decreased food intake, but the lorazepam withdrawal abstinence syndrome was much less intense and had a shorter latency to onset than the diazepam abstinence syndrome, which also included clonic and tonic-clonic convulsions and was lethal in two dogs. Furthermore, the diazepam withdrawal abstinence syndrome was biphasic, the first phase apparent by 24 hr and a second phase beginning at 48 hr, whereas the lorazepam syndrome was not. Diazepam suppressed the major signs of diazepam abstinence in a dose-related manner, but failed to completely suppress all signs of abstinence. CGS-8216, a pyrazoloquinoline benzodiazepine antagonist, precipitated abstinence in the diazepam-dependent dog, but did not precipitate tonic-clonic seizures. No abstinence syndrome was precipitated in the lorazepam-dependent dog. These results would suggest that whereas diazepam and lorazepam both cause physical dependence the two syndromes are not the same and, furthermore, that physical dependence on, and withdrawal from, diazepam involves at least two separate mechanisms with different selectivity for benzodiazepine agonists and antagonists.
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PMID:Physical dependence on diazepam and lorazepam in the dog. 613 1

Rats chronically treated with increasing daily doses of delta 9-tetrahydrocannabinol (delta 9-THC) for up to 5 or 10 days exhibit a withdrawal-like behavioural response when challenged with clomipramine, a potent inhibitor of serotonin (5-hydroxytryptamine) reuptake, at the time when the next injection of delta 9-THC was due. To determine whether this response is indeed a withdrawal syndrome, different groups of rats were injected IV twice daily for up to 5 days with either delta 9-THC, in doses increasing from 2-6 mg/kg, or polyvinyl-pyrrolidone (PVP), the vehicle in which delta 9-THC was suspended. On day 6, an acute dose of 6 mg/kg delta 9-THC was given 30 min before IP clomipramine (15 mg/kg). The total behavioural response, which included writhing, backward kicking, jumping, head shaking, and paw tremor, was attenuated in rats chronically treated with delta 9-THC, but not in rats which received an acute dose of PVP. These results lend further evidence to our hypothesis that chronically administered delta 9-THC produces a state of physical dependence in the rat.
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PMID:Attenuation of delta 9-tetrahydrocannabinol-induced withdrawal-like behaviour by delta 9-tetrahydrocannabinol. 626 50

A comparison of several methods for developing physical dependence to morphine was made. Male Sprague-Dawley rats were treated with morphine-admixed food (drug-admixed food, DAF; 0.5 and 1 mg/g food), morphine slow release emulsion (SRE; 75, 100 and 150 mg/kg) and morphine (75 mg) pellets. In the SRE and pellet methods, the typical signs of morphine toxicity, such as catatonia, exophthalmos and shallow respiratory movements, were observed 15-20 min after the treatment and these signs were maintained for 14-18 hr. In rats treated with SRE and pellets, plasma morphine levels reached a maximum 1 day after the morphine treatment, and subsequently decreased, while plasma morphine levels in rats treated with DAF increased treatment period-dependently. Withdrawal signs precipitated by naloxone (3 mg/kg, sc) in rats treated with DAF, SRE and pellets were characterized by loss of body weight, shaking, vocalization, diarrhea, ptosis, tooth-chattering, nose bleed, salivation and lacrimation. Naloxone-precipitated withdrawal signs reached a maximum 1-2 days after treatment with SRE and pellets, and were correlated with the duration of DAF treatment. Rats treated with DAF, SRE (150 and 225 mg/kg) and pellets for 3 days, manifested loss of body weight, diarrhea etc. after the morphine withdrawal. Maximum body weight loss in each group was 7-10% at 1-2 days after the morphine withdrawal. It was thus, concluded that physical dependence on morphine can be induced rapidly by these three methods. However, the SRE and pellet methods induced morphine toxicity and it was difficult to maintain physical dependence on morphine in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparison of three methods of inducing physical dependence to morphine in rats using short-term medication]. 654 77


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