A versatile procedure for rapid induction of narcotic addiction in the rat utilizing intravenous injections

Numan, Robert; Smith, Nelson; Lal, Harbans

doi:10.3758/bf03337520

Cited by 10 publications

(2 citation statements)

References 9 publications

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“…This schedule, as described in Table I , was employed throughout the experiment. As was previously reported [Numan et al, 1975;La1 and Numan, 19761 rats implanted with the indwelling cannula and perfused with saline for 10 days did not show wet-doglike body shakes during or after the saline perfusion (Table 2). However, when continuously perfused with morphine, the infused rats became narcotic dependent and, upon withdrawal, exhibited typical withdrawal signs (for review see Gianutsos et al, [1975]), such as hypothermia, body shakes, piloerection, ptosis, irritability, aggression and weight loss.…”

Section: A Morphine Dependence and Withdrawal Shakessupporting

confidence: 83%

“…Earlier results from exploratory experiments undertaken in laboratory animals [Lal et al, 1971a,b;Puri and Lal, 1973;Gianutsos et al, 1974;La1 and Numan, 1976;Martin et al, 19741 and human patients [Karkalas and Lal, 19731 were encouraging. The present study is a more expanded investigation of three butyrophenones and two phenothiazines that were tested in the presence and in the absence of naloxone in rats made morphine dependent by a continuous infusion technique described earlier [Numan et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

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A comparison of butyrophenone and tricyclic neuroleptics with narcotics in blocking withdrawal signs in rats continuously infused with morphine

Hynes

Lal

1981

Drug Development Research

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Hynes, Martin D. and Harbans Lal: A Comparison of butyrophenone and tricyclic neuroleptics in blocking withdrawal signs in rats continuously infused with morphine. Drug Dev. Res. 1:199-209, 1981. Narcotic dependence was established in male rats by continuous infusion of morphine given in increasing concentrations. Termination of the morphine infusion resulted in the reliable occurrence of body shakes. Narcotic drugs, morphine, fentanyl, and methadone, blocked withdrawal body shakes in a dose-dependent manner. The butyrophenone neuroleptics, haloperidol, benperidol, and azaperone, were also effective in reducing withdrawal body shakes at doses that do not produce side effects. Trifluoperazine and chlorpromazine, two tricyclic neuroleptics were effective in reducing withdrawal shakes only at high doses that produced side effects. The anti-withdrawal action of morphine, haloperidol, benperidol, and azaperone but not of chlorpromazine and trifluoperazine was antagonized by naloxone.

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Section: A Morphine Dependence and Withdrawal Shakessupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

A comparison of butyrophenone and tricyclic neuroleptics with narcotics in blocking withdrawal signs in rats continuously infused with morphine

Hynes

Lal

1981

Drug Development Research

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Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat

et al. 1981

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An intravenous infusion method is described for rapidly producing physical dependence in rats. Rats were infused with morphine or meperidine for 24 or 48 h at constant rates and the development of physical dependence was assessed by body weight loss after naloxone challenge. Naloxone challenge induced body losses that were dependent upon magnitude, rate and duration of infusion. The steady-state concentrations of morphine (4 mg/kg/h) in serum and meperidine (6 mg/kg/h) in plasma were 4 and 2.5 microgram/ml, respectively. Morphine concentration in the brain in the steady-state (40 mg/kg/h) was 0.7 micrograms 1 g and in the serum was proportional to the infusion rate. Maximum body weight loss was significantly correlated with total amount of infused morphine, but not with the steady-state concentration of the drug in the serum. These results suggest that total doses of infused morphine, not steady-state concentrations, are critical in producing body weight loss.

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Rapid induction and quantitation of morphine dependence in the rat by pellet implantation

Bhargava

1977

Psychopharmacology

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Four schedules of subcutaneous morphine pellet implantation were developed to render rats rapidly physically dependent on morphine. The schedules included implantation of four morphine pellets over a 3-day period (schedule 1), six morphine pellets over a 3-day period (schedule 2), six pellets over a 7-day period (schedule 3), and ten pellets over a 10-day period (schedule 4). Each morphine pellet contained 75 mg of morphine base. The degree of morphine dependence was quantitated by determining the median effective dose (ED50) of naloxone required to induce the stereotyped jumping response. Hypothermia and weight loss, during abrupt and naloxone-induced withdrawal, were also measured. Rats on schedule 4 exhibited a high degree of dependence on morphine as evidenced by an extremely low naloxone ED50 for the precipitated withdrawal jumping response, whereas schedules 1 and 2 produced a low degree of dependence as shown by high naloxone ED50's. Further evidence for a high degree of physical dependence on morphine is schedule 4 rats was indicated by their greater loss in body weight and greater hypothermic response after abrupt and after naloxone precipitated withdrawal compared with these responsed in the rats in the other three schedules. A correlation was found to exist between naloxone ED50 for the jumping response, body weight loss, and hypothermia observed during naloxone-induced withdrawal in morphine-dependent rats. These studies suggest that the implantation of four morphine pellets in the rat produces a mild degree of dependence and that caution should be exercised when making generalized conclusions about the biochemical correlations involved when four or less number of pellets, each containing 75 mg of morphine base, are used to induce morphine dependence in the rat.

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A versatile procedure for rapid induction of narcotic addiction in the rat utilizing intravenous injections

Cited by 10 publications

References 9 publications

A comparison of butyrophenone and tricyclic neuroleptics with narcotics in blocking withdrawal signs in rats continuously infused with morphine

A comparison of butyrophenone and tricyclic neuroleptics with narcotics in blocking withdrawal signs in rats continuously infused with morphine

Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat

Rapid induction and quantitation of morphine dependence in the rat by pellet implantation

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