Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous infusions were used to produce physical dependence upon ethanol in rats. The procedure proved to be safe, rapid, and reliable. Ethanol (30% v/v) was administered over a 7-day period. The mean daily dose ranged from 10--14 g/kg/day. Control rats were exposed to a comparable procedure except that saline, rather than ethanol, was infused. All ethanol treated rats that survived the intoxication period (n = 11) showed signs of physical dependence (moderate to severe, n = 8; mild, n = 3) following ethanol withdrawal. Saline treated rats (n = 8) did not show any of these symptoms. The most reliable ethanol withdrawal signs observed were: spontaneous seizure (n = 7), audiogenic seizure (n = 7), tremors (n = 6), tail stiffening (n = 10) and body rigidity (n = 9). These symptoms were analyzed in terms of their hour of onset and hour of maximum intensity following ethanol withdrawal. Application of the intravenous method for the study of ethanol self-administration is discussed.
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PMID:Induction of physical dependence upon ethanol in rats using intravenous infusion. 56 3

The new cognition-enhancing agent nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7) was assessed for dependence liability in rats using the DAF (drug admixed food) method and an intravenous self-administration system. In the physical dependence test, nefiracetam and codeine phosphate were administered to rats mixed with food for 43 days in a gradually increasing dosage schedule, followed by feeding a drug-free normal diet to detect signs of withdrawal. After the withdrawal, rats in the nefiracetam treated groups showed no withdrawal symptoms (e.g. body weight loss) and exhibited greater body weight gains than control. On the other hand, rats in the codeine phosphate treated group showed overt withdrawal symptoms (e. g. soft stool, diarrhea, vocalization) and a significant body weight loss, suggesting development of physical dependence on the drug. It was concluded that nefiracetam did not possess physical dependence liability in rats. In the reinforcement liability test, through an indwelling cannula implanted into the right jugular vein rats were allowed to self-administer nefiracetam, morphine hydrochloride or pentobarbital for 14 days. Saline was administered to negative control animals for the same period. The daily frequency of self-administration increased progressively with time in rats of the morphine hydrochloride and pentobarbital groups. In the nefiracetam groups, it remained comparable to or was even lower than that in the saline control group. When compared with the saline control, the group mean frequency of self-administration showed a tendency to be small for nefiracetam, whereas the morphine hydrochloride and pentobarbital showed greater frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug dependence study of the new cognition-enhancing agent nefiracetam in rats. 801 97

Intravenous zolpidem self-injection, and the concurrent development of physical dependence under conditions of continuous drug availability, was characterized in three baboons. Previously, under similar conditions, 1.0 mg/kg midazolam maintained low, but stable, daily rates of self-injection (e.g. less than 20 injections/day) over 30 or more days and resulted in the development of physical dependence in baboons. In the current experiments, saline and zolpidem (1.0 mg/kg) were available for self-injection under a fixed-ratio (FR-30) schedule of lever-pull responses with a 5 min time-out after each injection. Saline maintained only low levels of responding (i.e. less than five injections per day). Zolpidem maintained an orderly spaced within-day pattern of injections and daily rates of self-injection were higher than saline (i.e. 10 or more injections per day). Daily rates of zolpidem self-injection were relatively stable in two baboons, and increased over time in the third baboon. Substitution of saline for zolpidem produced a rapid decrease in responding that remained low (i.e. less than five injections per day) in all three baboons. Chronic self-injection of zolpidem produced an increase in responding maintained by food pellet delivery and an increase in body weights. Administration of flumazenil (0.1-1.0 mg/kg, i.v.) after at least 35 days of zolpidem self-injection produced postures and behavioral signs typical of a classic flumazenil-precipitated benzodiazepine withdrawal syndrome. Substitution of saline after chronic zolpidem self-injection produced a time-limited spontaneous withdrawal syndrome. Behavioral signs and postures were similar to those observed during flumazenil-precipitated withdrawal and were most prominent during the first 8 days after zolpidem was discontinued. Therefore, like midazolam, zolpidem maintained self-injection and physical dependence developed under conditions of long-term continuous availability.
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PMID:Zolpidem self-injection with concurrent physical dependence under conditions of long-term continuous availability in baboons. 983 41

This study utilises pharmacological functional magnetic resonance imaging (fMRI) to examine the neurobiological mechanisms through which nicotine produces dependence. Using an established regime to induce physical dependence to nicotine in rats (osmotic minipumps delivering 3.16 mg/kg/day nicotine for 7 days SC), animals were subsequently anaesthetised under urethane and positioned in a stereotaxic frame to allow collection of gradient echo whole brain images with a 4.7-T MRI spectrometer. Rats were initially scanned for 34 min (40 baseline image volumes, 1 volume per 51 s) then challenged with mecamylamine (1.0 mg/kg SC) or saline (1 ml/kg) and scanned for a further 68 min (80 image volumes). Mecamylamine precipitated highly significant positive changes in fMRI blood oxygen level dependent (BOLD) contrast that were predominantly localised to the NAc of nicotine-dependent rats. Saline-treated rats challenged with the same dose of mecamylamine exhibited similar but smaller increases in BOLD contrast although such changes were less defined around the NAc. Precipitated withdrawal also elicited statistically significant negative BOLD contrast changes in widespread cortical regions. These findings are consistent with previous neurochemical reports on decreases in dopamine in the NAc during nicotine withdrawal. This fMRI study further highlights the potential and power to image the neurobiological events during nicotine dependence.
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PMID:Imaging localised dynamic changes in the nucleus accumbens following nicotine withdrawal in rats. 1519 14