Importance of D1 and D2 receptors in the dorsal caudate-putamen for the locomotor activity and stereotyped behaviors of preweanling rats.

Dopaminergic compounds often affect the unlearned behaviors of preweanling and adult rats differently, although the brain regions underlying these age-dependent behavioral effects have not been specified. A candidate brain region is the dorsal caudate-putamen (CPu); thus, a goal of the present study was to determine whether D1 and D2 receptors in the dorsal CPu are capable of modulating the unlearned behaviors of preweanling rats. In Experiments 1 and 2, selective and nonselective dopamine agonists were bilaterally microinjected into the dorsal CPu on postnatal day (PD) 18 and both locomotor activity and stereotypy were measured. In Experiment 3, the functional coupling of D1 and D2 receptors was assessed by microinjecting the D1 agonist SKF-82958 and the D2/D3 agonist quinpirole either alone or in combination. In Experiments 4 and 5, quinpirole and the D1 receptor antagonist SCH-23390, or SKF-82958 and the D2 receptor antagonist raclopride, were co-administered into the dorsal CPu to further assess whether a functional D1 or D2 receptor system is necessary for the expression of quinpirole- or SKF-82958-induced behaviors. Results showed that selective stimulation of D1 or D2 receptors in the dorsal CPu increased both the locomotor activity and stereotypy of preweanling rats. Receptor coupling was evident on PD 18 because co-administration of a subthreshold dose of SKF-82958 and quinpirole produced more locomotor activity than either agonist alone. Lastly, the dopamine antagonist experiments showed that both D1 and D2 receptor systems must be functional for SKF-82958- or quinpirole-induced locomotor activity to be fully manifested. When the present data are compared to results from non-ontogenetic studies, it appears that pharmacological manipulation of D1 and D2 receptors in the dorsal CPu affects the behavior of preweanling and adult rats in a generally similar manner, although some important age-dependent differences are apparent. For example, D1 and/or D2 agonists preferentially induce locomotor activity, and not intense stereotypy, in younger animals.

Age-dependent effects of kappa-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate-putamen: an in vivo microdialysis study.

kappa-Opioid receptor stimulation attenuates psychostimulant-induced increases in extracellular dopamine in the caudate-putamen (CPu) and nucleus accumbens of adult rats, while reducing cocaine-induced locomotor activity and stereotyped behaviors. Because kappa-opioid receptor agonists (e.g., U50,488 or U69,593) often affect the behavior of preweanling rats in a paradoxical manner, the purpose of the present study was to determine whether kappa-opioid receptor stimulation differentially affects dopaminergic functioning in the CPu depending on age. In vivo microdialysis was used to determine whether U50,488 (5 mg/kg) attenuates cocaine-induced dopamine overflow in the dorsal CPu on postnatal day (PD) 17 and PD 85. In the microinjection experiment, cocaine-induced stereotyped behaviors were assessed in adult and preweanling rats after bilateral infusions of vehicle or U50,488 (1.6 or 6.4 microg per side) into the CPu. Results showed that U50,488 attenuated the cocaine-induced increases in CPu dopamine overflow on PD 85, while the same dose of U50,488 did not alter dopamine dialysate levels on PD 17. Cocaine also increased stereotyped behaviors (repetitive motor movements, behavioral intensity scores, and discrete behaviors) at both ages, but adult rats appeared to exhibit more intense stereotypic responses than the younger animals. Consistent with the microdialysis findings, bilateral infusions of U50,488 into the dorsal CPu decreased the cocaine-induced stereotypies of adult rats, while leaving the behaviors of preweanling rats unaffected. These results suggest that the neural mechanisms underlying kappa-opioid/dopamine interactions in the CPu are not fully mature during the preweanling period. This lack of functional maturity may explain why kappa-opioid receptor agonists frequently induce different behavioral effects in young and adult rats.

Effects of aspirin and related drugs in vitamin E-deficient rats.

Evidence from the literature indicates that in vitamin E-deficient animals prostaglandin (PG) synthesis in platelets is enhanced while it is decreased in the muscle and testis. In the present study the effects of aspirin, a known inhibitor of PG biosynthesis, on vitamin E deficiency signs in the rat were investigated. Administration of aspirin to vitamin E-deficient rats had no protective effect on fetal mortality, incisor depigmentation, body weight gain or red blood cell peroxidative hemolysis. Aspirin prevented the anemia and thrombocythemia observed in vitamin E-deficient rats. Aspirin, salicylic acid and a carbazole prostaglandin inhibitor exacerbated testis degeneration in vitamin E-deficient animals. Addition of aspirin to the diet more than doubled the vitamin E requirement for reversal of necrotizing myopathy.

Determination of xylitol in human urine by gas-liquid chromatography.

A rapid and specific method for the quantitative determination of xylitol in human urine has been developed. The method consists of the gas-liquid chromatographic analysis of the acetate ester derivative of the alditol in deionized urine using dulcitol as an internal standard. As little as 20 ng xylitol can be detected. At concentrations ranging from 25 to 400 micrograms/ml urine, the accuracy is +/- 4.0%.

Plasma activity of pyruvate kinase and glutamic oxalacetic transaminase as indices of myopathy in the vitamin E deficient rat.

Weanling rats were fed vitamin E deficient diets for 6 to 15 weeks and then given vitamin E orally for 4 days. Plasma obtained 1 day after the last dose was assayed for glutamic oxalacetic transaminase (GOT) and pyruvate kinase activity (PK). Administration of vitamin E resulted in reduction in activity of both enzymes. Plasma levels of alkaline phosphatase, lactic dehydrogenase, and bilirubin were unaffected by vitamin E and there was no histological evidence of liver degeneration. The number of phagocytized muscle fibers was greatly reduced by vitamin E treatment, but a substantial number of necrotic fibers were still present. With more prolonged (8 days) treatment, plasma PK and GOT levels were reduced to levels found in plasma of vitamin E replete animals and few degenerated muscle fibers could be observed. It was concluded that resolution of the necrotizing myopathy in vitamin E deficient rats is a rapid process and that the decreased activity of PK and GOT in plasma is a sensitive indicator of the resolution process. The decrease in plasma enzyme levels is an easily quantitated and reproducible biological response to vitamin E administration. Thus, this approach provides a basis for a sensitive and accurate bioassay for vitamin E activity.

Effects of a prolonged vitamin E deficiency in the rat.

Rats fed a vitamin E-deficient diet containing 10% "stripped" corn oil had reduced growth rate and elevated platelet count by 12 weeks of age, and a normocytic anemia with elevated reticulocytes by 16 weeks of age. After 5 months, rats became emaciated and developed kyphoscoliosis. Some rats developed skin ulcers and tremors, and mortality was high. Neuromuscular lesions included a chronic necrotizing myopathy and localized axonal dystrophy. There was also a selective activation of lysosomes in the central nervous system microcirculation. Liver ascorbic acid of deficient rats was the same as in those receiving vitamin E. Urinary excretion of p-hydroxyphenylpyruvate after a tyrosine load was also the same in deficient and control rats. It was concluded that neither vitamin C synthesis or utilization was affected the E-deficient rats.