Brain and serum levels of naloxone following peripheral administration

Striatal, hypothalamic and serum concentrations of naloxone were measured by a new high-performance liquid chromatographic procedure at various time up to 120 min following subcutaneous administration of 1, 5, and 10 mg naloxone hydrochloride/kg to rats. A dose-concentration relationship was evident throughout. Peak levels were observed at the first measurement time (15 min) and tissue values were consistently higher than concentrations in serum. The correlations between serum and brain naloxone levels suggests that in normal rats central concentrations of the drug can be extrapolated from serum concentrations.     

Genistein administration decreases serum corticosterone and testosterone levels in rats

The phytochemical flavonoid genistein has been shown to act as a potent competitive inhibitor of human adrenocortical 3beta-hydroxysteroid dehydrogenase and cytochrome P450 21-hydroxylase activities in vitro [J. Steroid Biochem. Molec. Biol. 2002; 80: 355-363]. In the present study, we evaluated the effects of large amounts of genistein continuously administered to weanling rats, particularly on steroidogenesis at the pubertal stage in vivo. Serum concentrations of free and total genistein were significantly higher in the 40 mg/kg genistein administration group when compared with the control group. In genistein administered rats, adrenal weight was significantly higher. Furthermore, a clear expansion of cells was observed in hematoxylin and eosin stained tissue at the zona fasciculata and zona reticularis of the adrenal cortex. However in the testis, no differences in weights or histologic changes were observed. Serum corticosterone concentration significantly decreased to 50% of control levels by 40 mg/kg genistein administration and testosterone also tended to decrease with this dose of genistein. On the other hand, although serum follicle stimulating hormone was unchanged, adrenocorticotropic hormone and luteinizing hormone levels increased with genistein administration. These results suggest a significant effect of genistein on steroidogenesis in the adrenal gland and testis of rats, and this effect appeared to be more evident on steroid production in adrenals than in testis in vivo.     

Effect of intraventricular administration of noradrenaline and dopamine on the levels of corticosterone in rats and denervation hypersensitivity resulting from intraventricular administration of 6-hydroxydopamine.

The effects of intraventricular administration of noradrenaline (NA) on the resting levels, stress-induced rises and dexamethasone-induced decreases of plasma corticosterone (B) were studied in rats. The effect of pretreatment with intraventricular administration of 6-hydroxydopamine (6-OHDA) on the effects of NA or dopamine (DA), which was injected intraventricularly, was also examined. The results obtained were as follows: 1) Intraventricular administration of 1.0 μg of NA did not cause a decrease in concentrations of plasma B. 2) Ten μg of NA injected intraventricularly resulted in a rise of the levels of plasma B. 3) The stimulating action of centrally administered NA was more marked when the pre-injection concentrations of B were lower. 4) Pretreatment with intraventricular administration of 6-OHDA facilitated the action of intraventricularly administered NA in the regulation of pituitary-adrenocortical functions. The result suggests a development of denervation hypersensitivity caused by the pretreatment. 5) Intraventricular administration of NA did not block stress-induced rises of plasma B. 6) Intraventricular administration of NA counteracted dexamethasone-induced decrements of plasma B. 7) This counteraction was enhanced by pretreatment with intraventricular administration of 6-OHDA. This also suggests a development of denervation hypersensitivity resulting from intraventricular administration of 6-OHDA. 8) Intraventricular administration of 1.0 μg of DA caused no change in the concentrations of plasma B in either control or 6-OHDA treated animals.     

Changes of serum and tissue amoxicillin levels following chlorpromazine administration in rats

Patients under treatment with chlorpromazine (CPZ) may need antibacterial administration. Amoxicillin is the most widely used antibacterial agent in dental infections. The aim of this study was to investigate the possible interactions between amoxicillin and CPZ and the eventual changes in amoxicillin levels using an experimental model in rats. Thirty male Wistar rats weighing 200-260 g were used for this study. They were divided into three groups: group A taking 15 mg/kg amoxicillin every 8 h for 4 days; group B taking amoxicillin as group A, and 1.07 mg/kg CPZ every 8 h for 4 days; and group C taking only CPZ in the same dose as group B. Drugs were given per os for 4 days, using a special catheter. The rats were sacrificed 2 h after the last dose. Antibacterial levels were estimated in blood serum, jaw bones, tongue and liver. An increase in the level of amoxicillin in serum as well as in tissues was observed in group B. No significant antibacterial activity of CPZ was detected. The increase in amoxicillin concentration in serum and jaws of group B was statistically significant in relation to group A.     

Intraperitoneal administration of choline increases serum glucose in rat: involvement of the sympathoadrenal system.

Intraperitoneal injection of choline (40, 80 or 120 mg/kg) produced a dose-dependent increase in serum glucose and choline levels in rats. The increases in serum glucose and choline were associated with an increase of serum insulin as well as plasma levels of epinephrine and norepinephrine. The increases in serum glucose and plasma catecholamine concentrations induced by choline (120 mg/kg) were blocked by pretreatment with the ganglionic nicotinic receptor antagonist hexamethonium (15 mg/kg), but were not affected by pretreatment with atropine (5 mg/kg). The choline-induced rise in serum insulin was blocked by pretreatment with atropine and with hexamethonium each. The increase in serum glucose evoked by choline (120 mg/kg) was blocked by alpha-adrenoceptor blockade and bilateral adrenalectomy each. Blockade of beta-adrenoceptor by propranolol or chemical sympathectomy by 6-hydroxydopamine failed to alter the hyperglycemic response to choline. These results show that choline, a precursor of the neurotransmitter acetylcholine, increases serum glucose and insulin levels. The effect of choline on serum insulin is mediated by both muscarinic and nicotinic acetylcholine receptors, whereas the effect of choline on serum glucose is mediated solely by nicotinic receptors. The stimulation of adrenal medullary catecholamine release and subsequent activation of alpha-adrenoceptors apparently mediates the hyperglycemic effect of choline.     

Tyrosine administration decreases serum prolactin levels in chronically reserpinized rats

The injection of tyrosine, 200 mg/kg, decreased serum prolactin levels and elevated hypothalamic (and striatal) concentrations of two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, in chronically reserpinized rats. Tyrosine administration had none of these effects in otherwise untreated rats, and did not block the increase in serum prolactin that occurred 4 hours after a single injection of reserpine. As anticipated, the injection of dopa decreased serum prolactin in all rats. Valine, another large neutral amino acid, did not modify serum prolactin in chronically reserpinized animals. Since prolactin secretion is normally inhibited by dopamine released from the hypothalamus, reserpine treatment probably elevates serum prolactin by depleting the hypothalamus of dopamine. Our data suggest that tyrosine injection suppresses serum prolactin levels in chronically reserpinized rats by enhancing the synthesis and release of hypothalamic dopamine. Thus, administration of tyrosine, dopamine's dietary precursor, can alter physiologic functions that depend on dopamine.