oxymorphone and Body-Weight

We have previously shown that (+/-)-3,4-methylenedioxymethamphetamine (MDMA) treatment from postnatal days (P)11 to P20 leads to learning and memory deficits when the animals are tested as adults. Recently, the club drug 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) has gained popularity.. Due to the similarities between MDMA and 5-MeO-DIPT and the substitution of 5-MeO-DIPT for MDMA, the purpose of this study was to compare the developmental effects of these drugs.. Within a litter, animals were treated from P11 to P20 with either MDMA, 5-MeO-DIPT, or saline.. MDMA-treated animals showed increased anxiety in a measure of defensive marble burying, as well as deficits in spatial and path integration learning. 5-MeO-DIPT-treated animals showed spatial learning deficits; however, there were no deficits observed in spatial memory or path integration learning. 5-MeO-DIPT-treated animals also showed hyperactivity in response to a challenge dose of methamphetamine.. The results show that treatment with either 5-MeO-DIPT or MDMA during development results in cognitive deficits and other behavioral changes but the pattern of effects is distinct for each drug.

Topics: Aging; Animals; Anxiety; Body Weight; Cues; Female; Hallucinogens; Learning; Lighting; Maze Learning; Memory; Motor Activity; N-Methyl-3,4-methylenedioxyamphetamine; Oxymorphone; Pregnancy; Rats; Rats, Sprague-Dawley

Endogenous opioids seem to regulate hypothalamic gonadotropin release in both males and females, as evidenced by the effects of opioid agonists and antagonists on LHRH release and reproductive hormone levels. The effects of long-term oral administration of opioid analgesics on reproductive function have not been well characterized.. The reproductive effects of oxymorphone, a potent opioid agonist, were investigated in male and female Crl:CD(SD) IGS BR rats at oral doses of 0, 5, 10, and 25 mg/kg/day (25 animals/sex/group). Males were treated for approximately 9 weeks (mated after 4 weeks of dosing). Females were treated for 14 days before mating, and through Gestation Day (GD) 7. Estrous cycling was evaluated during the premating period. On GD15, pregnancy status and the numbers of corpora lutea, implantation sites, live and dead embryos were determined. Epididymal and testicular sperm counts and epididymal sperm motility and morphology were evaluated in males.. Two males given 25 mg/kg/day died. Behavioral changes and deficits in body weight gain occurred at all doses. There were no effects of oxymorphone on reproductive function or sperm parameters in males. The estrous cycle was prolonged in females given 25 mg/kg/day (mean of 5.3 vs. 4.3 days in controls). A small, but consistent decrease in the numbers of corpora lutea (with associated decreases in implantation sites and embryos) occurred in females given > or =10 mg/kg/day. There were no effects on mating or fertility in females.. Oxymorphone seems to partially inhibit ovulation in female rats, with no significant effects on male reproductive outcome.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Body Weight; Dose-Response Relationship, Drug; Female; Fertility; Male; Maternal Exposure; No-Observed-Adverse-Effect Level; Organ Size; Ovulation; Oxymorphone; Paternal Exposure; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction

Despite their long history of chronic use, little information is available regarding the carcinogenicity of opioid analgesics. Oxymorphone is a potent morphinan-type mu-opioid analgesic used for treatment of moderate-to-severe pain. Oxymorphone was tested for carcinogenicity in Crl:CD IGS BR rats and CD-1 mice. Oxymorphone hydrochloride was administered orally once daily for 2 years to rats at doses of 2.5, 5 and 10 mg/kg/day (males) and 5, 10 and 25 mg/kg/day (females), and mice at 10, 25, 75 and 150 mg/kg/day (65 animals per sex per group; 100 animals per sex in controls). In rats, survival was generally higher than controls in oxymorphone-treated groups, attributable to lower body weight gain. In mice, survival was generally higher than controls in females at all doses and males given < or = 25 mg/kg/day but lower in males given > or = 75 mg/kg/day due to a high incidence of obstructive uropathy. Opioid-related clinical signs and reduced body weight gain occurred in both species throughout the study. Nonneoplastic findings associated with oxymorphone pharmacology included ocular and pulmonary changes in rats considered secondary to inhibition of blinking and mydriasis, and antitussive activity, respectively, and urinary tract and renal findings in mice considered secondary to urinary retention. There was no target organ toxicity, and no increase in any neoplastic lesions attributed to oxymorphone. Plasma oxymorphone levels achieved in these studies exceeded those in patients taking high therapeutic doses of oxymorphone (Area under the curve [AUC(0-24 h)] values up to 5.6-fold and 64-fold in rats and mice, respectively). Oxymorphone is not considered to be carcinogenic in rats or mice under the conditions of these studies.

Topics: Analgesics, Opioid; Animals; Body Weight; Carcinogenicity Tests; Carcinogens; Dose-Response Relationship, Drug; Eating; Eye; Female; Humans; Leukocyte Count; Lung; Male; Mice; Oxymorphone; Rats; Rats, Sprague-Dawley; Time Factors; Toxicity Tests, Chronic; Urogenital System

The use of mice in biomedical research is increasing, largely due to the production and use of genetically engineered animals. Providing postoperative pain control in mice presents many challenges, and long-acting analgesic preparations would be advantageous for this species. A single subcutaneous injection of a liposome-encapsulated (LE) preparation of oxymorphone was compared with multiple injections of buprenorphine or saline in outbred mice undergoing splenectomy. Control groups were given isoflurane alone or isoflurane and an injection of LE oxymorphone but did not undergo surgery. The following parameters were evaluated for 5 days after surgery and were compared with presurgical baseline data for each group: food and water consumption, body weight, ethographic score, and voluntary exercise on a running wheel. Ethographic scores indicated less postsurgical pain in both groups of mice that received either analgesic preparation compared with mice that received only saline. However, mice given LE oxymorphone had superior postoperative recovery, as measured by wheel-running distance and body weight gain, compared with mice given buprenorphine or saline. Mice undergoing splenectomy had significant decreases in body weight, food and water consumption, voluntary exercise, and other normal behaviors. Administration of liposomal oxymorphone at the time of surgery improved postsurgical recovery as measured by these parameters compared with multiple injections of buprenorphine or saline alone. Administration of LE oxymorphone at the time of surgery improved postsurgical recovery, as measured by these parameters.

Topics: Analgesics, Opioid; Animals; Animals, Outbred Strains; Behavior, Animal; Body Weight; Buprenorphine; Drinking; Eating; Injections, Subcutaneous; Laboratory Animal Science; Liposomes; Male; Mice; Mice, Inbred ICR; Oxymorphone; Pain; Pain Measurement; Physical Conditioning, Animal; Specific Pathogen-Free Organisms; Splenectomy

Cystometry was performed in 12 dogs under oxymorphone and acepromazine restraint. A detrusor reflex occurred in 10 of 12 dogs (83%). Mean threshold pressure and volume were 31 cm H2O and 22 ml/kg, respectively. Tonus limb II varied inversely with threshold volume. Threshold volume varied directly with body weight; threshold pressure was independent of body weight.

Topics: Acepromazine; Animals; Body Weight; Dogs; Drug Combinations; Female; Hydromorphone; Immobilization; Male; Muscle Contraction; Muscle Tonus; Muscle, Smooth; Oxymorphone; Pressure; Reflex; Urinary Bladder; Urinary Catheterization