The Effect of Melanotrophin Release Inhibiting Factor (Mif) and Cyclo (Leu‐gly) on the Tolerance to Morphine‐induced Antinociception in the Rat: A Dose‐response Study

Bhargava, Hemendra N.

doi:10.1111/j.1476-5381.1981.tb09152.x

Cited by 43 publications

(7 citation statements)

References 30 publications

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“…For in stance. the role of central dopamine receptors in morphine tolerance-dependence has been studied in the rat using behavioral methods [Bhargava, 1980a. 1981b: Gianutsos et al.…”

Section: Fig 8 Change In Colonic Temmentioning

confidence: 99%

Pharmacodynamics and Kinetics of Loss of Tolerance and Physical Dependence on Morphine Induced by Pellet Implantation in the Rat

Villar¹,

Bhargava²

1992

Pharmacology

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The decay characteristics of tolerance and physical dependence on morphine induced by a pellet implantation procedure were determined in male Sprague-Dawley rats. Rats were implanted subcutaneously with 6 morphine pellets during a 7-day period. The pellets were removed, and at various times thereafter tolerance to the analgesic and hyperthermic effects of morphine was measured by determining the response in rats implanted with morphine and placebo pellets. Similarly, the physical dependence was assessed by monitoring withdrawal signs following an injection of naloxone. A high degree of tolerance developed to the analgesic and hyperthermic effects of morphine. Similarly, a high degree of physical dependence also developed as evidenced by a high incidence of jumping response, teeth chattering and production of fecal boli induced by injections of naloxone. In addition, loss of body weight and body temperature also occurred. The analgesic and hyperthermic response to morphine recovered very gradually. There was no significant difference in the analgesic and hyperthermic responses to morphine on day 4 after the pellet removal in rats implanted with morphine and placebo pellets. The decay of tolearance was linear with time for the analgesic effect (r = 0.98) and for the hyperthermic effect (r = 0.93). The change in symptoms of physical dependence on morphine with time depended on the specific symptom monitored. The average number of jumps and teeth chattering decreased with time in a linear fashion with r values of 0.98 and 0.99, respectively. However, the number of fecal boli and wet dog shakes increased linearly with time (r = 0.97). The recovery of loss of body weight was also linear with time. Thus, it is clear that fecal boli and wet dog shakes, which increase in number as the dependence decays, are signs of a low degree of dependence. The results suggest that different central or peripheral mechanisms may be operating in different withdrawal symptoms. These studies may prove to be useful when studying the mechanisms involved in the induction and reversibility of tolerance and dependence processes, and in long-term effects of opiates at a time when the tolerance and physical dependence is no longer evident.

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“…For in stance. the role of central dopamine receptors in morphine tolerance-dependence has been studied in the rat using behavioral methods [Bhargava, 1980a. 1981b: Gianutsos et al.…”

Section: Fig 8 Change In Colonic Temmentioning

confidence: 99%

Pharmacodynamics and Kinetics of Loss of Tolerance and Physical Dependence on Morphine Induced by Pellet Implantation in the Rat

Villar¹,

Bhargava²

1992

Pharmacology

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“…The analgesic effect was measured by using a tailflick apparatus as described before [20][21][22][23]. The tailflick latencies to thermal stimulation were determined before and at various times up to 300 min after an injection of morphine (8 mg/kg, i.p.).…”

Section: Quantification O F the Analgesic And Hyperthermic Responses mentioning

confidence: 99%

Dizocilpine(MK-801) Blocks Tolerance to the Analgesic but Not to the Hyperthermic Effect of Morphine in the Rat

Bhargava

Matwyshyn

1993

Pharmacology

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The effect of dizocilpine (MK-801), an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in the rat. Tolerance to morphine in male Sprague-Dawley rats was induced by implanting subcutaneously 6 morphine pellets during a 7-day period. Two schedules of intraperitoneal injections of MK-801 were used. In one, the drug was injected once a day, and in the other it was injected twice a day. The doses of MK-801 were 0.03, 0.1 and 0.3 mg/ kg. In the treatment once a day, MK-801 blocked the development of tolerance to the analgesic effect of morphine, but there was no dose-dependent effect. In the treatment twice a day, MK-801 produced a dose-dependent inhibition of tolerance to the analgesic effect of morphine. Higher doses of MK-801 produced high mortality. MK-801 given once a day or twice a day failed to affect the tolerance to the hyperthermic effect of morphine. In both schedules of MK-801 treatment, the highest dose of MK-801 resulted in high mortality. It is concluded that MK-801 is selective in blocking the tolerance to the analgesic effect of morphine in the rat.

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“…The elucidation of the role played by D 2 -Rs during the expression and development of tolerance to morphine antinociception needs further investigation. However, it is known that chronic morphine treatment is associated with the development of behavioural supersensitivity mediated by dopamine receptors (Puri and Lal, 1973;Gianutsos et al, 1974;Iversen and Joyce, 1978;Ritzman et al, 1979;Bhargava, 1980Bhargava, , 1981. Whether D 2 -R activation induced by quinpirole during the development of tolerance prevents this supersensitivity should be clarified.…”

Section: Discussionmentioning

confidence: 99%

Dopamine receptor mechanism(s) and morphine tolerance in mice

Zarrindast

Dinkoub²,

Homayoun³

et al. 2002

J Psychopharmacol

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Based on our previous demonstration of the involvement of dopamine-2 (D2) dopamine receptors in morphine antinociception, we examined the role of D2 dopamine receptors in the expression and development of tolerance to morphine antinociception in mice. Tolerance to morphine antinociception was assessed by the tail-flick response after the administration of morphine (50 mg/kg) once daily for 3 days. The D2 dopamine receptor agonist, quinpirole (0.01, 0.02 and 0.03 mg/kg), but not the D2 dopamine receptor antagonist, sulpiride (12.5, 25 and 50 mg/kg), increased morphine antinociception in morphine non pre-exposed mice. The response of quinpirole was decreased by the lower doses of sulpiride. Both quinpirole and sulpiride decreased the expression and development of tolerance to antinociception induced by morphine (1.5, 3 and 6 mg/kg). The effect of quinpirole on the expression and development of tolerance, was reduced by a lower and per se non-effective dose of sulpiride. It was concluded that D2 dopaminergic receptors may play a part in the expression and development of tolerance to the antinociceptive effect of morphine.

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The Effect of Melanotrophin Release Inhibiting Factor (Mif) and Cyclo (Leu‐gly) on the Tolerance to Morphine‐induced Antinociception in the Rat: A Dose‐response Study

Cited by 43 publications

References 30 publications

Pharmacodynamics and Kinetics of Loss of Tolerance and Physical Dependence on Morphine Induced by Pellet Implantation in the Rat

Pharmacodynamics and Kinetics of Loss of Tolerance and Physical Dependence on Morphine Induced by Pellet Implantation in the Rat

Dizocilpine(MK-801) Blocks Tolerance to the Analgesic but Not to the Hyperthermic Effect of Morphine in the Rat

Dopamine receptor mechanism(s) and morphine tolerance in mice

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