Sex Differences in the Induction of Physical Dependence on Pentobarbital in the Rat

Suzuki, Tsutomu; Koike, Yoko; Yoshii, Toshitaka; Yanaura, Saiζo

doi:10.1254/jjp.39.453

Cited by 24 publications

(17 citation statements)

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“…In this study, physical dependence on pentobarbital was established with a drug admixed food method (12)(13)(14)19), which has been successfully used in the past for the development of physical dependence on pentobarbital in Sprague-Dawley rats (16,17). The drug dosage schedule used in the present study was the same as that used in an earlier study (17).…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, severe physical dependence on pentobarbital as manifested by withdrawal convulsions had not been shown in rodents. However, reports from several laboratories have now documented the development of marked physical dependence on pentobarbital (15)(16)(17)(18).…”

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“…A procedure was used that can produce severe physical dependence (17). For preparing the drug admixed food, sodium pentobarbital (Tokyo kasei Kogyo, Tokyo, Japan) was mixed with a normal powdered food (CA-1, Japan Clea, Tokyo, Japan) in a mortar (13,14).…”

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“…Rats of each strain were divided into two groups, the pentobarbital-treated group (n=7) and the control (non-treated) group (n=6). The rats were chronically treated with pentobarbital according to the method of Suzuki et al (17). The concentration of pentobarbital in the food was gradually increased, as shown in Table 1.…”

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Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats.

et al. 1987

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Abstract-Fischer 344 (F344), Lewis (LEW), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were chronically fed food containing pentobarbital on an escalating drug dosage schedule over a period of 47 days. During treatment, the growth curve in LEW, SHR and WKY rats was suppressed as compared with the respective controls. Motor incoordination was evaluated by a rotarod per formance test. The ranking of the motor incoordination was as follows: WKY>>j LEW>SHR>F344.After substitution of normal food for the pentobarbital admixed food, various signs of pentobarbital withdrawal occurred. The withdrawal signs from pentobarbital in F344, LEW and SHR rats were mild as compared with those in WKY rats. The order of the severity of withdrawal signs in four inbred strains was parallel to that for motor incoordination. These results suggest that the differences between strains in withdrawal can be attributed to differences in the degree of chronic CNS depression produced by pentobarbital. Genetic differences in tolerance and physical dependence to several drugs have been reported. Among the more commonly used inbred strains of mice, the C57BL/6 strain seems to develop a greater degree of physical dependence on morphine (sensitivity to naloxone-induced jumping) than the DBA/2 strains (1). There have been several genetic studies of tolerance to and physical de pendence on ethanol in inbred mice. Grieve et al. (2) reported that the C57BL strain developed tolerance much faster than does the DBA strain, and the C57BL strain showed brief and mild withdrawal signs in comparison with the DBA strain. Goldstein and her collaborator (3, 4) showed a differential resistance to withdrawal seizures in the C57BL strain. These experiments suggest that genotype is an important determinant of the degree of tolerance to and physical dependence on ethanol and morphine.Acute effects of barbiturates have also been examined in genetic studies. C57BL mice are known to be more sensitive than DBA and BALB mice to pentobarbital (5-7). Recently, Khanna et al. (8) reported that pentobarbital and barbital sleep times for spontaneously hypertensive (SHR) rats were significantly less than for Wistar Kyoto (WKY) rats, and barbiturate blood levels at awakening were significantly higher in SHR than in WKY rats. Very few studies of physical dependence on barbiturates have examined genetic

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Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats.

et al. 1987

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“…2). With this procedure, the animals became severely dependent on pen tobarbital (28,29), methaqualone (40, 41) and diazepam (42), and withdrawal con vulsions can be induced. These results sug gest that an escalating dose schedule is one more important factor for developing physi cal dependence on CNS depressants in rats.…”

Section: Physical Dependence 1 Opioidmentioning

confidence: 99%

Pharmacological studies on drug dependence in rodents: Dependence on opioids and CNS depressants.

Suzuki

1990

Jpn.J.Pharmacol

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Abstract-Physicaland psychic dependence on opioids and CNS depressants in rodents were examined using the drug-admixed food (DAF) method.A comparison of several methods for developing physical dependence on opioids was made. The DAF method has the advantage of rapidly inducing a high degree of physical dependence without causing morbidity or mortality. When morphine-dependent rats were pretreated with several opioids, naloxone-precipitated weight loss was suppressed in a dose-dependent manner.A procedure for the development of severe physical dependence on CNS depressants was also established. Drug con centrations were rapidly increased until animals showed moderate to severe CNS depression, and then this condition was maintained for at least 10 days. With this procedure, animals became severely dependent on CNS depressants. Another technique, intermittent infusion, was developed that has been used to quantify short acting CNS depressant dependence potential.The sedative effects of pentobarbital were used as an index in the determination of the injection intervals.These results suggest that the DAF method and the new approaches are useful tools for assessing the physical dependence potential of new drugs. Moreover, oral self-administration and weight pulling procedures were utilized along with the DAF method. Pro cedures for the oral self-administration of opioids and CNS depressants were estab lished. Opioid-dependent rats pulled the weight to obtain the DAF even though they had free access to normal food. This weight-pulling procedure may be useful for assessing the degree of reinforcing effects for drugs in rats. I. Physical dependence 1. OpioidOn the basis of many years of study with the opioids, well defined methods have been developed for the assessment of physical de pendence.Physical dependence on opioids can quickly be induced in rodents by a variety of techniques, including implantation of mor phine pellets (1-3), infusion of opioids (4-6), treatment with slow release emulsion (SRE) of opioids (7,8) and implantation of a re servoir of morphine solution (9). The drug admixed food (DAF) method developed by Yanaura et al. (10,11) is an easy way to produce physical dependence on opioids in rodents without the stress of surgery or injection. It is well-known that the degree and severity of physical dependence are influenced by dose, frequency (dosing inter val) and duration of drug administration and that the frequency is the most important factor (12). From these points of view, we examined physical dependence on opioids using the DAF method. a) Effects of dose: Rats were chronically administered 5 doses of morphine (0.0625, 0.125, 0.25, 0.5 and 1.0 mg/g of food) for 7 days by the DAF method. physical dependence on morphine was car ried out using withdrawal signs precipitated by naloxone (3.0 mg/kg, s.c.) challenge. The average daily morphine intake for 7 days was 5. 29, 10.58, 21.49, 38.19 and 76.94 mg/kg/ day in animals treated with morphine at doses of 0.0625, 0.125, 0.25, 0.5 and 1.0 mg/g of food, resp...

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Effects of pentobarbital and progesterone on random ratio responding in male and female rats

et al. 1987

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Intact male and ovariectomized female rats were trained to lever press under a random ratio (RR) schedule of food reinforcement. Effects of different doses of pentobarbital (1-16 mg/kg) and progesterone (10-80 mg/kg) on response output were studied. Low doses of pentobarbital increased responding, high doses decreased responding. Sex differences were observed in the rate-decreasing effects of high doses of pentobarbital. Progesterone increased the response rate of ovariectomized females, but did not affect responding in intact males.

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Sex Differences in the Induction of Physical Dependence on Pentobarbital in the Rat

Cited by 24 publications

References 8 publications

Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats.

Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats.

Pharmacological studies on drug dependence in rodents: Dependence on opioids and CNS depressants.

Effects of pentobarbital and progesterone on random ratio responding in male and female rats

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