Hypothalamic self-stimulation during the abstinence syndrome in morphine-dependent rats

Rats with lateral hypothalamic self-stimulation were treated chronically with morphine (30 injections in the course of 15 days) in doses increasing stepwise from 20 to 120 mg/kg per injection. Morphine facilitated self-stimulation from the 9th injection. Both short-term abstinence (16-18 hours) and cessation of the narcotic resulted in inhibition of the response. Full suppression of self-stimulation occurred under the administration of nalorphine, morphine antagonist, in a dose of 5 mg/kg.     

Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats

The aim of our study was to investigate the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats. Male Wistar rats were divided among (i) control, saline-treated, and (ii) thioacetamide-treated groups (TAA(300) (300?mg/kg body mass); TAA(600) (600?mg/kg); and TAA(900) (900?mg/kg)). The daily dose of thioacetamide (300?mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or 3 times (TAA(900)), on subsequent days. Behavioral manifestations were determined at 0, 2, 4, 6, and 24?h, while electroencephalographic changes were recorded 22-24?h after the last dose. General motor activity and exploratory behavior, as well as head shake, auditory startle reflex, placement, and equlibrium tests were diminished in the TAA(600) and TAA(900) groups compared with the control, and were absent in the TAA(900) group 24?h after treatment. Corneal, withdrawal, grasping, and righting reflexes were significantly diminished in the TAA(900) group compared with the control. Mean electroencephalographic power spectra density was significantly higher in TAA(300) and TAA(600) and lower in the TAA(900) group by comparison with the control. Only a score of 3 (mean dominant frequency?≤ 7.3?Hz and δ relative power?≥ 45%) was observed in the TAA(900) group. Thioacetamide induces encephalopathy in rats in a dose-dependent manner. A dose of 900?mg/kg TAA may be used as a suitable model of all stages of hepatic encephalopathy.     

Symptoms of neonatal abstinence syndrome. Case report

A case of the neonatal narcotic abuse syndrome is presented. A newborn baby additionally suffered from the congenital infection. Marked symptoms of narcotic withdrawal required an administration of the opiates and tranquillizers for three weeks.     

Analog of neuropeptide FF attenuates morphine abstinence syndrome.

The octapeptide FLFQPQRFamide (neuropeptide FF or F8Fa) may play a role in opiate dependence and subsequent abstinence syndrome. Previously, NPFF precipitated opiate abstinence syndrome, while IgG from NPFF antiserum attenuated subsequent naloxone-precipitated abstinence signs in dependent rats. The peptide desamino YFLFQPQRamide (daY8Ra) was synthesized as a possible NPFF antagonist. At a dose of 600 ng ICV, daY8Ra significantly attenuated (p less than 0.001) the number of abstinence-like signs subsequently induced by 10 micrograms NPFF ICV, suggesting that daY8Ra does have antagonist activity against NPFF. Pretreatment of morphine-dependent rats with the same dose of daY8Ra also significantly attenuated (p less than 0.001) the abstinence signs subsequently precipitated by 10 micrograms naloxone ICV. Pretreatment with 600 ng of NPFF itself, or of NPFF modified at the N-terminal only (daY9Fa), failed to attenuate subsequent naloxone-precipitated abstinence, suggesting that the C-terminal modification is critical for NPFF antagonist activity. It should be noted, however, that higher doses of daY8Ra (2 micrograms or more) can precipitate some abstinence signs in a manner similar to NPFF.     

Cerebrospinal fluid from morphine-dependent rats precipitates opiate abstinence syndrome

Cerebrospinal fluid (CSF) was withdrawn from opiate-dependent rats following six hours of abstinence. It was infused into the third ventricle of opiate-dependent rats, precipitating immediate abstinence signs. The effect was similar to that of infusing the opiate antagonist naloxone, suggesting that opiate-dependent organisms may secrete an endogenous opiate antagonist substance. CSF withdrawn from non-dependent rats failed to precipitate an abstinence syndrome in morphine-dependent recipients. Conversely, CSF withdrawn from opiate-dependent rats following six hours of abstinence failed to precipitate an abstinence syndrome in non-dependent recipients. The active factor in the CSF is probably a peptide since it is filterable through a 10,000 MW filter and its activity is destroyed by three different proteolytic enzymes.     

Excretion of catecholamines in development of the opium and alcohol abstinence syndrome and in post-abstinence period

Excretion of catecholamines has been studied in patients with opium narcotic and alcoholic dependence in developmental dynamics of the opium and alcoholic abstinence syndrome and in the postabstinence period. It has been revealed that 8-10 h after cessation of the psychoactive substances (the preabstinence period) the level of excretion of adrenaline [A], dioxyphenylalanine [DOPA], dopamine [DA] and, to the greatest extent, of noradrenaline [NA] especially in patients with alcoholic dependence decreases in comparison with the control variant. As compared to the control variant the acute form of abstinence syndrome (1-3 days after cessation of the psychoactive substances is characterized by the higher level of the A and DA excretion and the lower level of the NA excretion (especially in patients with opium narcotic dependence). As compared to the preabstinence period under conditions of the acute abstinence syndrome there is an essential increase in the level of the A, NA, DOPA and DA excretion. As compared to the control variant the postabstinence period (10-20 days after cessation) is characterized by the lower level of the NA excretion, especially in patients with alcoholic dependence, and of DOPA. The level of DA decreases in patients with alcoholic dependence. As compared to the acute abstienence syndrome the postabstinence period differs by the lower level of the A, NA (especially in patients with alcoholic dependence), DOPA (only inpatients with alcoholic dependence) and of DA excretion.     

Behavioral characterictics of ISIAH rat strain

This work was performed in hypertensive ISIAH and normotensive WAG rat strains. The latter was used as a control group. The general evaluation of behavior of the ISIAH and WAG rats tested in the open field, in the light-dark test, in the sound stress test, and in the fatigue test showed that the motor and exploratory activity provoked by an unfamiliar environment was much higher in the ISIAH rats as compared to the control WAG strain. Spontaneous locomotor activity of the ISIAH rats in the home cage was significantly lower as compared to the control WAG strain. This finding suggests that the ISIAH rats are hyperreactive in an novel environment. It is concluded that the hypertensive ISIAH rats are significantly different from the control WAG rats not only in the arterial blood pressure level, but also in behavioral patterns.     

Anxiety level during morphine abstinence correlates with the status of nitrergic system in the rat hippocampus

Opiate addiction is accompanied by long-term structural and functional changes in brain regions persisting during abstinence, this status being an experimental model of the aberrant neuroplasticity. Nitric oxide is known to be involved in mechanisms of psychopathological events during opiate abstinence. In this study, indices of a nitregic system (nitric synthase activity--NOS, nitrites and nitrates concentration--NOx-) were measured in the rat brain region during morphine abstinence. Prior to this, the rats were tested for anxiety in an elevated plus maze. NOS activity increased in hippocampus 3 days after morphine withdrawal, while NOx--6 days after withdrawal. No changes of the nitrergic system could be revealed in other brain regions under study. Six days (but not 3 days) after morphine withdrawal, rats visited the open arms of the plus maze more frequently and spent more time in these arms as compared with respective controls. The data suggest that nitrergic system changes in the hippocampus may be involved in molecular mechanisms of behavioural alteration during morphine abstinence in rats.     

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.     

Morphological manifestations of anthracycline cardiomyopathy in the ventricular myocardium of the rat

Cardiomyopathy and plastic contractile myocardial insufficiency were simulated in Wistar rats by an anthracycline antibiotic rubomycin. The myocardium in conditions of DNA-dependent RNA synthesis suppression was studied using polarization, electron microscopy and the method of cardiomyocyte isolation. During anthracycline cardiomyopathy in the absence of necrotic and necrobiotic myocardial injuries there was a smaller depression of cardiomyocyte population and their nuclei in the right ventricle (23 and 22% respectively) than in the left ventricle (38 and 39% respectively). It was concluded that a smaller amount of cardiomyocyte population was in the phase of intensive protein synthesis in the right than in the left ventricular myocardium.     

Inhibition of abstinence syndrome in opiate defendent mice by cyclo (His-Pro)

Intracerebral administration of cyclo (His-Pro), the postulated metabolite of thyroliberin (TRH, pGlu-His-Pro-NH₂) inhibited the naloxone induced withdrawal responses in morphine dependent mice. Mice were rendered dependent on morphine by the subcutaneous implantation of a pellet (containing 75 mg of morphine free base) for three days. Six hours after pellet removal, the naloxone ED₅₀ for the jumping response was found to be higher in mice injected with cyclo (His-Pro) compared with that of vehicle controls. Similarly, the hypothermic response observed following 50 μg/kg of naloxone given given 6 h after pellet removal or that seen with 100 μg/kg of naloxone given 24 h after pellet removal from morphine-dependent mice was inhibited by cyclo (His-Pro). Previously, we have shown similar results with TRH on the morphine abstinence syndrome. It appears, therefore, that cyclo (His-Pro) may be the active metabolite of TRH and analogs of cyclo (His-Pro) may be useful in blocking the symptoms of the opiate abstinence syndrome.     

Behavioral and neurochemical investigation of circadian time-place learning in the rat

The ability to form an association between the time and the place of food availability, namely time-place learning, is presumably important for survival. The present study was designed to examine time-place learning and to identify exogenous and endogenous factors that may affect this behavior in rats. In an initial experiment, rats displayed poor time-place behavior and appeared to prefer the feeder that was closer to the center aisle and water supply. When these cues were minimized in a subsequent experiment, rats consistently displayed the time-place discrimination by exhibiting food anticipatory activity (FAA) at the correct location prior to each meal time. These rats also showed significant correlations between the level of FAA and the amount of dopamine turnover (the dihydroxyphenylacetic acid/dopamine ratio) in the nucleus accumbens and paraventricular nucleus of the hypothalamus, indicating possible involvement of regional dopaminergic activity in time-place behavior. No correlation was found for norepinephrine, epinephrine, or serotonin. In addition, the correlation between FAA and dopamine turnover was not found when rats were entrained to only one meal per day. Together, the data suggest that rats can learn the time-place discrimination under proper experimental conditions and that dopamine may play a role in the expression of this behavior.     

The relation of abstinence analgesia to the development of cardiac disorders in the ethanol withdrawal syndrome in rats

Ethanol was administrated intragastrically (25%, w/v) to Wistar male rats. They received 7-10 g ethanol/kg b.wt. daily in 2 fractional doses for 6 days. In 20-24 hours after the last ethanol administration behavioral and neurological signs of withdrawal syndrome and pain latent period were measured. Analgesia was determined using the tail flick and hot plate tests. Two days later systolic function of the isolated perfusing heart and creatine phosphokinase outflow were examined. Rats had longer latent pain period than in control. Heart perfusion revealed a decrease of systolic pressure, dp/dt of systolic and diastolic pressure, increase of enzyme outflow. Kendall's correlation analysis revealed a positive relationship between intensity of withdrawal symptoms and analgesia index in the hot plate test (tau = +0.343, p. 0.01) and a lack of relationship in the tail flick test. There was negative relationship between the analgesia index and the indices of heart disorders. It is proposed that analgesia index can be used as a predictor of the cardiac muscle injury caused by the alcoholic abstinent syndrome.