Interactions of angiotensin IV and oxytocin on behaviour in mice.

INTRODUCTION: Angiotensin (Ang) IV enhances learning and memory in rats but there are strain differences in its effects in mice. Oxytocin (OT) also influences learning and memory in rats and mice and, in the light of the proposed effects of Ang IV on oxytocinase, the hypothesis that the effects of Ang IV on cognition in mice involve OT was tested. MATERIALS AND METHODS: The effects of Ang IV and OT, alone and combined, were determined in rat isolated uterine smooth muscle and in object recognition and forced swim tests in BKW mice. RESULTS: Ang potentiated the contractile effects of OT in the uterus. Neither peptide had any effect on object recognition nor locomotor activity. Ang IV had no effect in the forced swim test but abolished the effects of OT. CONCLUSIONS: Ang IV influences the actions of OT in vitro and in vivo, possibly by inhibition of oxytocinase, but the lack of effect of Ang IV on object recognition in BKW mice is unlikely to be a consequence of a deficiency endogenous OT. Unlike OT, Ang IV alone has no effect on learned helplessness in the forced swim test, an effect often used to predict potential antidepressant efficacy in humans.     

Rheological characterisation of dextran-concanavalin A mixtures as a basis for a self-regulated drug delivery device.

The rheological characterisation of glucose sensitive mixtures containing dextran and concanavalin A (con A) with and without glucose, was undertaken using oscillatory rheometry at 20 and 37 degrees C so that comparative data could be gathered in the linear viscoelastic (LVE) range. Measurements for a series of mixtures showed that complex viscosity is a function not only of the con A concentration but of the content and molecular weight of the dextran used. The extent of liquefaction on addition of glucose also depended on these factors. The tan delta profiles confirmed the change from semi-solid towards fluid behaviour. This occurs when glucose effects dismantling of the three-dimensional structure of the dextran-con A system by competitive binding to the glucose receptors in the protein. For the mixtures studied, the changes occurred between contents of 0 and 1% (w/w) glucose at 20 and 37 degrees C and form a useful basis for the formulation of a self-regulating delivery device for the control of hyper-and hypoglycaemia in diabetes.     

Cross-reactivity of selected compounds in the Abbott TDx cannabinoid assay

Immunoassay procedures, both enzyme immunoassay and radioimmunoassay, continue to be widely used to screen samples for recent marijuana use by analyzing the urine samples for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta 9-THC-9-COOH) (the major urinary metabolite of delta 9-tetrahydrocannabinol [delta 9-THC]). Using commercially available immunoassay reagents, the cross-reactivity of the antiserum utilized in Abbott's TDx cannabinoid assay (a fluorescence polarization immunoassay) was evaluated. This cross-reactivity was evaluated against a group of cannabinoids and noncannabinoid phenolic constituents of Cannabis, some cannabinoid metabolites, and other agents that appear in normal urine samples. In general, the antiserum was equally reactive toward 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid, its glucuronide, and the corresponding delta 8-isomer, which was the acid moiety utilized in standards and controls of the assay prior to January, 1990. Reduced binding to the antiserum was observed with hydroxylated derivatives of delta 9- and delta 8-THC, and the other cannabinoids, in general, exhibited limited binding potentials toward the antibody. For the noncannabinoid constituents, no binding was observed at the highest concentrations evaluated (40 mg/L).     

Hypolipidemic activity in rodents of phenobarbital and related derivatives

A series of 5-alkyl-5-phenylbarbituric acid analogues were shown to be potent hypolipidemic agents in rats and mice at 20 mg/kg/day. This dose is lower than that required for hypolipidemic activity for clofibrate and nicotinic acid derivatives in rodents and man. These new derivatives reduced both serum cholesterol and triglyceride levels in rodents by either the oral or intraperitoneal route of administration. Previous studies have demonstrated that similar heterocyclic compounds, i.e. cyclic imides, glutarimides and hydantoins are potent hypolipidemic agents in rodents. The barbituric acid derivatives probably interfered with de novo synthesis of cholesterol and fatty acids in the early steps since the agents inhibit the activities of ATP-dependent citrate lyase and acetyl-CoA synthetase. Triglyceride synthesis may be blocked since the agents inhibited the rate limiting enzyme, sn-glycerol-3-phosphate-acyl-transferase. Rat tissue lipids especially cholesterol and triglycerides were reduced after 14 days treatment. Fecal lipids were increased in cholesterol and phospholipid content by selected compounds. The rat serum lipoprotein after 14 days drug administration showed reduced VLDL-cholesterol and HDL-triglyceride contents. The modulation of the lipid content of the serum lipoproteins by the barbituric acids suggest that these agents may be helpful in treating clinical hyperlipidemic disease states.     

Evaluation of drugs for treatment of urinary bladder dysfunction in conscious rats with intact pelvic nerve and after resection of the left pelvic nerve

We studied the effects of drugs used for treatment of bladder dysfunction in conscious rats with intact pelvic nerves and also in rats at one or two weeks after nerve decentralization on the left side. Bladder contraction accompanying micturition was continuously induced by infusion of solution at a constant rate. When the effects of oxybutynin (3 mg/kg, i.p.) and terodiline (3 and 10 mg/kg, i.p.) on the cystometrogram were studied for about 2 hr, these drugs shortened and then prolonged the micturition interval (MI), but atropine (1 and 5 mg/kg, i.p.), butylscopolamine (20 mg/kg, i.p.) and nifedipine (3 mg/kg, i.p.) exhibited only a shortening effect on the MI. After injection of oxybutynin (10 mg/kg, i.p.), solution dribbled from the urethra for about 30 min. Terodiline (3 mg/kg) caused ischuria in the rats one week after resection of the left pelvic nerve, but not in the rats two weeks after surgery. Physostigmine (0.3 mg/kg, i.p.) improved micturition in the rats one week after surgery, but the effect was not evident in the rats with intact pelvic nerves. It was found that the drugs used for treating failure to store or expel urine exhibited a beneficial effect on micturition in rats with intact pelvic nerves and also in rats one week after nerve decentralization, respectively.     

Development of tolerance to the CNS effects of aminoglutethimide in mice

Initially, there is a high incidence of CNS-depressant side-effects when the aromatase inhibitor, aminoglutethimide, is used in the treatment of patients with advanced breast cancer. Tolerance to these effects develops with continued dosing. This study examines the development of tolerance to various indices of CNS depression with the drug in mice. Single doses of aminoglutethimide induced a dose-dependent depression of spontaneous locomotor activity, rotarod performance, righting reflex and body temperature and a dose-related antileptazol activity. On repeated dosing with the drug, tolerance to these various activities occurred. The tolerance was found to be dose-dependent in the rotarod and righting reflex tests and time-dependent in the locomotor and body temperature tests. Although the results do not allow a determination of whether this clearly demonstrated phenomenon in the mouse is primarily functional or dispositional, the slow onset (14 days) for complete tolerance may be indicative of a functional mechanism.