u-50488 and Weight-Gain

Research has demonstrated that intake of palatable carbohydrates and fats enhanced morphine-induced analgesia (MIA) in Sprague-Dawley rats. To determine if the effects of palatable foods on nociceptive responses would generalize to other strains of animals and other opioid agonists, the present experiments investigated whether intake of palatable foods would: a) alter MIA in Long-Evans rats, and b) alter analgesia produced by drugs acting at kappa opioid receptors. In experiment 1, adult male Long-Evans rats were fed Purina chow alone or chow and either a 32% sucrose solution, a 0.15% saccharin solution, or hydrogenated vegetable fat. Using a tail-flick apparatus, nociceptive responses, measured as percent maximal possible effect (%MPE), were examined after morphine administration [0.0, 1.0, 3.0, and 6.0 mg/kg subcutaneously (SC)]. %MPEs varied directly as a function of dose and were significantly greater for rats fed chow and either sucrose or fat than for rats fed chow alone or chow and saccharin. Experiment 2 compared the analgesic effect of the kappa opioid receptor agonist U50,488H (0, 5.0, 10.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and a 32% sucrose solution. Administration of U50,488H led to analgesia. However, %MPEs did not vary directly as a function of dose. %MPEs of rats fed chow and sucrose were significantly greater than those of rats fed chow alone after injections of 10.0 and 20.0 mg/kg U50,488H. Experiment 3 compared the analgesic effect of U50,488H (5.0, 10.0, 15.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and either a 0.15% saccharin solution or hydrogenated vegetable fat. Administration of U50,488H led to analgesia. However, %MPEs did not vary directly as a function of dose or as a function of diet. %MPEs of rats fed chow and fat were significantly greater than those of rats fed chow alone after injection of 5.0 mg/kg U50,488H.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Analgesics, Opioid; Animals; Diet; Dietary Fats; Eating; Energy Metabolism; Male; Morphine; Pain Measurement; Pain Threshold; Pyrrolidines; Rats; Receptors, Opioid, kappa; Receptors, Opioid, mu; Sucrose; Weight Gain

To determine the effects of chronic perinatal exposure to a kappa opioid agonist on the neurochemical and motor development of rat offspring, osmotic pumps containing trans-(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U-50,488H), 79 mg/ml, or vehicle were implanted into anesthetized pregnant female rats. On postnatal day 10, the nucleus accumbens (NAc) of male offspring were dissected and assayed for dopamine (DA) receptors. Male offspring from other litters were injected subcutaneously with the D2 agonist quinpirole, 0.05 mg/kg, the D1 agonist SKF 38393, 10 mg/kg, or 0.9% saline vehicle. Their locomotor activity was then monitored for 1 h. The binding of DA D1 and D2 receptors was significantly increased by 26% and 90%, respectively, in the NAc of 10-day-old offspring exposed to U-50,488H. There was a significant, 52%, decrease in the locomotor response to quinpirole by 10-day-old offspring exposed to U-50,488H. Exposure to U-50,488H had no significant effect on the locomotor response to SKF 38393 at this age. The results indicate that perinatal exposure to a kappa agonist alters the development of brain DA receptors and DA-mediated motor behavior. The data suggest that motor deficits observed in offspring exposed to opioids in utero may involve brain kappa opioid receptor mechanisms.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Ergolines; Feeding Behavior; Female; Litter Size; Male; Motor Activity; Nucleus Accumbens; Pregnancy; Prenatal Exposure Delayed Effects; Pyrrolidines; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Opioid, kappa; Weight Gain