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

Abstract

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.

Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat

“…ACTH assay. In experiments involving measurement of plasma ACTH levels, polyethylene tubing for collecting blood was inserted into the jugular vein under pentobarbital (30 mg/kg) anesthesia administered by intraperitoneal injection, as described previously (Nakaki et al, 1981). In order to administer agents directly into the bilateral hypothalami, 26 gauge needles were inserted into the bilateral anterior hypothalami by a previously described method (Shintani et al, 1993), following insertion of the polyethylene tubing.…”

Mitragynine Attenuates Morphine Withdrawal Effects in Rats—A Comparison With Methadone and Buprenorphine

“…Various methods have been established to model morphine withdrawal in rats including implantation of morphine pellet (55, 56, 69-71), infusion method via implantation of intravenous catheters (72,73), subcutaneous mini osmatic pumps (74,75), drinking morphine solution containing water or sucrose (76)(77)(78), morphine-admixed food (79), or subcutaneous injection (80)(81)(82)(83) and intraperitoneal route (54, 84,85). However, all these methods have certain disadvantages.…”

Physical Dependence and Plasma Concentrations of Morphine in Rats

“…Morphine, well known for its potential to cause physical dependence [5], is a typical representative of dependence producing drugs and various methods have been established in rats to develop physical dependency. For example, in an invasive infusion method, rats implanted with intravenous catheters were treated with morphine at 4 mg/kg/h by continuous infusion or 2-8 mg/kg/infusion by intermittent infusion at intervals of 1 hour for 24-72 h [6,7] and rats implanted subcutaneous with osmotic mini pumps were treated with morphine at 0.7 mg/kg/h for 72 h [8]. Via the subcutaneous route, rats were injected with morphine at 15-55 mg/kg in a dose-increasing manner once daily for 5 days [9] and at 10 mg/kg twice daily for 5 days [10] or 14 days [11].…”