Effect of 6-hydroxydopamine on dark adaptation in the rat retina

6-Hydroxydopamine administered intravitreously to light-adapted rats appears to prevent the recovery of retinal sensitivity during subsequent dark adaptation through its interaction with the photochemical mechanisms.     

Effect of 6-hydroxydopamine on neuropeptides in the rat female genitourinary tract

The occurrence and distribution of neuropeptide Y has been determined in the rat female genitourinary tract by radioimmunoassay and chromatographic analysis. Within the bladder, higher concentrations of neuropeptide Y were found in the trigone (48.8±5.2 pmol/g) than in the dome (36.0±2.1 pmol/g). In the genital tract, highest concentrations were identified in the vagina (41.4±2.1 pmol/g). Treatment of rats with 6-hydroxydopamine resulted in significant depletion of neuropeptide Y concentrations in both parts of the bladder, together with vagina, uterine horn and fallopian tube. No change was observed in the cervix, uterine body and ovary. Concentrations of vasoactive intestinal polypeptide were unaffected by treatment with 6-hydroxydopamine except in the area of the cervix where concentrations rose from 64.1±5.7 pmol/g to 133.6±15.1 pmol/g (p<0.05). There was a generalised, but statistically insignificant rise in substance P concentrations.     

The effect of exogenous L-carnitine on fat diet-induced hyperlipidemia in the rat

In rats receiving a fat diet (75% Altromin R and 25% olive oil) ad libitum for 15 hours, an orally administered dose of 500 mg/kg L-carnitine produces: an increase in serum carnitine and acetyl-carnitine levels; a decrease in serum triglyceride (TG) and free fatty acid (FFA) levels; a normalization of the heart and liver carnitine pattern; a reduction of myocardial neutral lipase (NL) activity, without affecting lipoprotein lipase (LPL) of the heart. Under these experimentally-induced conditions, L-carnitine stimulates the excretion of acyl groups as acyl-carnitines with the urine. Acylcarnitines are practically absent from the urine of control animals.     

Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice

LDL receptor-deficient (LDLR(-/-)) mice fed a Western diet exhibit severe hyperlipidemia and develop significant atherosclerosis. Apolipoprotein E (apoE) is a multifunctional protein synthesized by hepatocytes and macrophages. We sought to determine effect of macrophage apoE deficiency on severe hyperlipidemia and atherosclerosis. Female LDLR(-/-) mice were lethally irradiated and reconstituted with bone marrow from either apoE(-/-) or apoE(+/+) mice. Four weeks after transplantation, recipient mice were fed a Western diet for 8 weeks. Reconstitution of LDLR(-/-) mice with apoE(-/-) bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in accumulation of apoE and apoB in the aortic wall. Plasma lipid levels were unaffected when mice had mild hyperlipidemia on a chow diet, whereas IDL/LDL cholesterol levels were significantly reduced when mice developed severe hyperlipidemia on the Western diet. The hepatic VLDL production rate of mice on the Western diet was decreased by 46% as determined by injection of Triton WR1339 to block VLDL clearance. Atherosclerotic lesions in the proximal aorta were significantly reduced, partially due to reduction in plasma total cholesterol levels (r=0.56; P<0.0001). Thus, macrophage apoE-deficiency alleviates severe hyperlipidemia by slowing hepatic VLDL production and consequently reduces atherosclerosis in LDLR(-/-) mice.     

Effects of 6-hydroxydopamine at birth on the development of hypertension in the rat

New-born rats treated daily with 6-hydroxydopamine (150 μg/g for 14 days after birth) produced a widespread and permanent destruction of both peripheral and central sympathetic neurones. The development of genetic hypertension was almost completely prevented by this treatment with 6-hydroxydopamine. However, the development of deoxycorticosterone/NaCl hypertension, although retarded, was not prevented by this treatment. The results point to a central involvement of noradrenergic neurones in the development of hypertension in the rat.     

Effect of 6-hydroxydopamine on the gene expression of Na+/Ca2+ exchanger in the rat heart

The Na+/Ca2+ exchanger (NCX) is an important component of the process of excitation-contraction coupling in the heart muscle. The level of gene expression as well as transport activities of this membrane structure is changed under pathological conditions like ischemic injury, myocardial infarction or diabetes. In this work we focused on the question whether the adrenergic modulation affects gene expression of the NCX in rat hearts. NCX mRNA levels were studied in the left cardiac atrium (divided into ganglionic and nonganglionic part) and also in the left ventricle of rats treated with 6-hydroxydopamine (6-OHDA) in control and stressed conditions. We have shown that administration of 6-OHDA decreases mRNA levels of NCX in both ganglionic and nonganglionic part of the left atrium and also in the left ventricle. This effect was not altered under combined administration of 6-OHDA and single immobilization stress. These data suggest that an activation of the adrenergic system can potentiate gene expression of the cardiac NCX.     

Effect of neonatal 6-hydroxydopamine treatment on audiogenic seizures

Subcutaneous injection of 6-hydroxydopamine (6-OHDA) in newborn audiogenic rats resulted in an increase in convulsive seizure intensity and a decrease in norepinephrine concentration in the cerebral cortex and the spinal cord. In addition, norepinephrine concentration in the brainstem (pons-medulla) was increased. Dopamine concentration in all brain regions studied was unchanged. The results suggest that norepinephrine exerts its modulatory influence on convulsive seizures by an action in either the spinal cord, the cerebral cortex, or both.     

Desmethylimipramine pretreatment prevents 6-hydroxydopamine induced somatostatin receptor reduction in the rat hippocampus.

Several studies have shown anatomical and functional interconnections between catecholaminergic and somatostatinergic systems. To assess whether somatostatin (SS) may act presynaptically on catecholamine neurons, SS receptors were measured using radioligand test-tube binding assays on synaptosomes from hippocampus and frontoparietal cortex--areas that are innervated by catecholaminergic neurons with different densities and that have a high number of SS receptors--from control and 6-hydroxydopamine (6-OHDA)-treated rats. Intracerebroventricular (i.c.v.) injection of the catecholamine neurotoxin 6-OHDA (0.78 mg free base/kg of body weight in saline with 0.1% ascorbic acid) lowered hippocampal and frontoparietal cortical noradrenaline (NA) and dopamine (DA) levels at 1 week following the injection. Pretreatment of rats with desmethylimipramine (DMI) (40 mg/kg, intraperitoneal) prevented the drop in NA levels, but was not effective in attenuating DA depletion in the two brain areas studied. Treatment with 6-OHDA lowered the number of 125I-Tyr11-SS receptors in the hippocampus (130 +/- 19 vs. 266 +/- 16 fmol/mg protein, P < 0.001), whereas in the frontoparietal cortex a non significant 20% reduction in receptor number was found. The dissociation constants of 125I-Tyr11-SS binding to synaptosomes from frontoparietal cortex (0.65 +/- 0.06 vs. 0.60 +/- 0.04, P not significant) and hippocampus (0.44 +/- 0.04 vs. 0.63 +/- 0.14, P not significant) were similar in control and treated groups. Pretreatment with DMI reversed up to 80% of the effect of 6-OHDA on hippocampus SS receptors. DMI alone had no observable effect on the number and affinity of SS receptors. The 6-OHDA and the DMI treatment did not affect SLI levels in the brain areas studied. These results suggest that a portion of the hippocampal SS receptors may be localized presynaptically on the noradrenergic and dopaminergic nerve terminals.     

Effect of acute and chronic deprivation of catecholaminergic system activity induced by 6-hydroxydopamine on the behavior of the rat

On 202 male rats of Wistar line, a study was carried out of the effect of chronic and acute deprivations of the brain CA-systems activity resulting from administration of 6-OHDA on investigating behaviour and learning. Chronic deprivation of CA-systems activity by neonatal administration of 6-OHDA (100 mg/kg subcutaneously) and their acute deprivation by intracerebral administration of 6-OHDA to adult rats (150 mkg in each lateral ventriculus) was accompanied by similar deep changes of behaviour. Both forms of deprivation reduced the investigating activity of the animals in the open field. In both cases, the above 6-OHDA dozes sharply impeded the learning of animals with emotionally negative reinforcement, with no significant influence on learning with emotionally positive reinforcement. Both forms of deprivation of CA-systems activity weakened the reaction of frustration elicited by a sharp reduction of food reinforcement.     

The influence of 6-hydroxydopamine on the development and inducibility of drug metabolism in rat liver

6-Hydroxydopamine (6-OHDA) pretreatment of rats in the first 4 days of life considerably enhances the low hepatic ethylmorphine N-demethylation rate in 9 and 16 day old rats, whereas the higher rates in adult rats are not influenced. After 6-OHDA treatment the age differences in ethylmorphine N-demethylation rate disappear. The induction of ethylmorphine N-demethylation by phenobarbital is markedly enhanced by neonatal 6-OHDA pretreatment in 16 to 60 day old rats, whereas in 9 day old rats this synergistic action is not detectable. Unlike ethylmorphine N-demethylation, hepatic 7-ethoxy-coumarin 0-deethylation rate is only slightly or not at all influenced by 6-OHDA pretreatment. The basic activities in 9 day and rats are enhanced, the induction by phenobarbital in the same age-group is decreased. In other age-groups neither basic activities nor inducibility are influenced by 6-OHDA pretreatment. Hepatic cytochrome P-450 concentrations in 33- and 60 day old control rats do not differ from those in 6-OHDA-pretreated animals. Phenobarbital treatment increases the P-450 content; this induction effect is enhanced after 6-OHDA pretreatment, but not as markedly as with ethylmorphine N-demethylation.     

Cerebral intraventricular 6-hydroxydopamine prevents vascular changes in the mineralocorticoid hypertensive rat

The effect of cerebral intraventricular administration of 6-hydroxydopamine (6-OHDA) on blood pressure and vascular smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-treated rats was assessed. Rats treated with 6-OHDA and DOCA had significantly lower systolic blood pressures (142 +/- 8 mm Hg) than rats treated with DOCA alone (185 +/- 5 mm Hg). After 5 weeks of DOCA treatment, femoral arteries and aortae were excised from these rats, cut helically into strips, and placed in a muscle bath to record isometric force. Dose-response curves to serotonin were shifted to the left in femoral arteries from DOCA-treated rats compared to both control and 6-OHDA-DOCA-treated rats (ED50: DOCA = 6.8 X 10(-8) M, control = 27.9 X 10(-8) M, 6-OHDA-DOCA = 13.4 X 10(-8) M). Arachidonic acid, the prostaglandin precursor, produced greater maximal contractions in femoral artery strips of DOCA-treated rats (358 +/- 56 mg) than in those from controls (115 +/- 31 mg). The maximal response to arachidonic acid in arteries from 6-OHDA-DOCA rats (203 +/- 78 mg) was not different from control values. Ouabain produced a greater maximal response in aortic strips from DOCA rats (658 +/- 165 mg) compared to those from control (196 +/- 72 mg) or 6-OHDA-DOCA (309 +/- 87 mg) rats. We conclude that increased vascular responsiveness to serotonin, arachidonic acid, and ouabain in DOCA hypertensive rats is secondary to a central action of the mineralocorticoid.