Detail of "76-99-3"

Reference

Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats

Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats. Moerschbaecher, Joseph M.; Mastropaolo, John; Winsauer, Peter J.; Thompson, Donald M. (Med. Cent., Louisiana State Univ., New Orleans, LA, USA). J. Pharmacol. Exp. Ther., 230(3), 541-9 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) In the presence of a stimulus above the center lever, monkeys and rats were required to complete 1 or 2 fixed-ratios on the center lever. Completion of the ratio turned off the center-lever stimulus and produced a stimulus above each of the 2 side levers. If the completed ratio was high, a response on the left lever produced a food pellet. If the ratio was low, a response on the right lever produced food. Errors produced a brief timeout. In monkeys, d-SKF 10047 [14198-28-8] either increased slightly or had no effect on response rate on the center lever, whereas it increased errors in a dose-related manner. In rats, both dl-SKF 10047 [7313-95-3] and cyclazocine [3572-80-3] produced a dose-related decrease in response rate and an increase in errors. The putative kappa agonist ethylketocyclazocine methanesulfonate [60183-11-1] produced similar effects in both the monkey and rat. At doses that decreased rate of responding, accuracy was unaffected, except at the highest dose that virtually eliminated responding. Unlike any of the other drugs tested, ethylketocyclazocine decreased rate by producing a dose-related pause at the start of the session rather than by altering the local rates of responding. In monkeys, the mu agonists morphine [57-27-2] and methadone [76-99-3] produced dose-related decreases in response rate, primarily due to sporadic pausing. Across this same range of doses neither drug affected errors, except at the high doses, at which relatively small decreases were obtained. In contrast, in the rat, morphine produced a dose-related decrease in response rate and an increase in errors. At several lower doses errors were increased, whereas response rate was unaffected. The effects of buprenorphine [52485-79-7] also differed between the species. In the monkey, doses as high as 3.2 mg/kg had no effect on the discriminative performance. In the rat, buprenorphine decreased rate and increased errors in a manner similar to that of morphine. The data suggest that the putative mu, kappa and sigma agonists studied exert greater differential effects on the accuracy of a discrimination in monkeys than in rats. The results are consistent with the notion that, in monkeys, opioids with activity at the putative sigma receptor exert disruptive effects on the accuracy of discriminations, an action not shared by prototypical mu and kappa agonists at doses that produce comparable rate-decreasing effects.

Acute and subchronic effects of methadone on the blood hormonal levels of pregnant and nonpregnant Charles River CD-1 mice

Acute and subchronic effects of methadone on the blood hormonal levels of pregnant and nonpregnant Charles River CD-1 mice. Bui, Quang Q.; Tran, Minhtam B.; West, William L. (Coll. Med., Howard Univ., Washington, DC 20059, USA). Pediatr. Pharmacol., 3(2), 69-78 (English) 1983. CODEN: PPHAD4. ISSN: 0270-322X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Blood levels of ACTH [9002-60-2], FSH [9002-68-0], and estriol [50-27-1] were measured throughout the estrous cycle and estriol was detd. at different stages during pregnancy in Charles River CD-1 mice treated with 10 mg/kg-day of methadone [76-99-3] or vehicle (physiol. saline). Animals received 1 dose in a const. vol. (10 mL/kg) per day s.c. of either methadone or saline. Blood samples of nonpregnant mice were collected 1 h after the 1st dose for acute effects and 1 h after the last dose treatment for subchronic effects. The acute administration of methadone in nonpregnant mice produced an increase in ACTH level throughout the estrous cycle whereas subchronic treatment reduced ACTH level by 51%. Acute treatment did not alter the estriol or FSH levels whereas subchronic treatment significantly lowered estriol by 17% and FSH by 79%. Methadone injected beginning on day 1 of gestation and continued through day 15 did not produce any effect on maternal body wt. or food consumption but resulted in an increase in resorption sites and decrease in implantation sites. The estriol levels in control pregnant mice were 19.8, 54.8, and 109.1 ng/mL on days 1, 10, and 15 of gestation, resp. A significant redn. of 18.8% and 35.2% in estriol was assocd. with methadone treatment by days 10 and 15 of gestation, resp. Methadone, by affecting several hormonal levels in both pregnant and nonpregnant CD-1 mice, may be responsible for some of the adverse effects on reprodn. encountered in this species.