Central histaminergic stimulation of corticosterone and hyperlipemic responses after chronic ethanol consumption in rats

The consumption of ethanol in a 10% solution for 3 weeks produced a negligible increase in corticosterone secretion in the rat but raised the levels of free fatty acid (FFA) in the serum. Mepyramine insignificantly antagonized and cimetidine intensified the corticosterone response. Histamine and the H₁- and H₂-receptor agonists, 2-pyridylethylamine (PEA) and dimaprit significantly raised the serum corticosterone levels in chronically alcoholized rats. Mepyramine antagonized and cimetidine increased the ethanol-induced hyperlipemia. Histamine, PEA and dimaprit considerably increased the serum FFA levels in alcoholized rats. After withdrawal of ethanol, histamine and dimaprit induced a marked hyperlipemic effect, whereas PEA did not increase the serum FFA concentration.These results indicate that in chronically alcoholized rats the central histaminergic system interacts with ethanol in regulation of the serum FFA level. After the ethanol withdrawal central H₁-receptors do not respond to H₁-agonist stimulation.     

Central histaminergic stimulation of hyperlipemic response in rats under stress

In rats subjected to a mild stress of immobilization histamine, the H₁-receptor agonist 2-pyridylethylamine (PEA), and the H₂-receptor agonists 4-methyl histamine (4-MeHA) and impromidine administered intracerebroventricularly (i.c.v.) 1 h prior to stress, intensified the stress-induced increase in serum free fatty acid (FFA) levels. Impromidine was far more potent than histamine and its agonists in increasing hyperlipemia in stressed rats. The hyperlipemic response to histamine was abolished by i.c.v. pretreatment of rats with mepyramine, a H₁-receptor antagonist, but was unchanged in rats pretreated with cimetidine or metiamide, H₂-receptor antagonists. The increase in serum FFA levels induced in stressed rats by PEA was abolished by mepyramine but the hyperlipemic responses to 4-MeHA and impromidine were not antagonized by cimetidine.These results suggest that central H₁-receptor mediate the histamine-stimulated hyperlipemic response in stressed rats.     

Naloxone antagonizes a central histaminergic stimulation of corticosterone secretion in rats

The interaction of central opioid receptors with histaminergic stimulation of the hypothalamo-pituitary-adrenocortical axis, evaluated indirectly through corticosterone secretion, was investigated in conscious unstressed rats. To avoid any possible direct action on the adrenal cortex, all drugs were given intracerebroventricularly (i.c.v.). Histamine, 2-pyridylethylamine (PEA), a histamine H₁-receptor agonist, and 4-methyl-histamine (MeHA) and dimaprit, the H₂-receptor agonists, considerably increased the serum corticosterone levels 1 h after adminstration. Naloxone, an opioid receptor antagonist, almost abolished the corticosterone response to PEA and considerably reduced the responses to MeHA, dimaprit and histamine. The maximum inhibitory effects of naloxone on corticosterone responses induced by histamine and histamine agonists were comparable with those of the H₁-and H₂-receptor antagonists, mepyramine and cimetidine.These results strongly suggest that a major part of the histaminergic stimulation of the hypothalamopituitary-adrenal axis is mediated by central opioid receptorsThe study was supported by the Polish Academy of Sciences, grant No 06.03.     

Interference of clonidine and α-methyl-p-tyrosine with stress and central histaminergic stimulation of the corticosterone response in rats

In conscious rats clonidine given intracerebroventricularly 1 h prior to a mild stress of immobilization intensified the stress-induced increase of pituitary-adrenocortical response, measured indirectly through corticosterone concentration in blood serum. The corticosterone response to clonidine was abolished by i.c.v. pretreatment of rats with yohimbine, an ₂-adrenergic antagonist, and was antagonized by pretreatment with phenoxybenzamine, an ₁-adrenergic antagonist. Clonidine intensified also the corticosterone response induced in stressed rats by i.c.v. injected histamine, 2-pyridylethylamine (PEA), a H₁-receptor agonist, and dimaprit, a H₂-receptor agonist.The depletion of brain catecholamines by -methyl-p-tyrosine (-MT) considerably increased the corticosterone response to stress but did not substantially change the response to histamine, PEA and dimaprit in stressed rats.These results suggest that clonidine increases the corticosterone secretion induced by a mild stress and histamine and histamine H₁ and H₂ agonists mainly through the activation of central ₁-adrenoceptors. The increase by -MT of the stress-induced corticosterone response may indicate the inhibitory role of central catecholamines in the pituitary-adrenocortical response to stress in rats.     

Influence of central neuronal histamine on the pituitary-adrenocortical activity stimulated by neurotransmitters

The effect of brain neuronal histramine and its receptors on monoaminergic stimulation of the hypothalamic-pituitary-adrenal (HPA) activity, measured indirectly through corticosterone secretion, was investigated in conscious rats. Pretreatment with -fluoromethylhistidine, (-FMH) a histamine synthesis inhibitor, did not markedly affect the increase in serum corticosterone levels induced by intracerebroventricular (icv) injection of muscimol, a GABA_A receptor agonist and noradrenaline, an - and -adrenergic agonist, and slightly diminished the corticosterone response to isoprenaline, a -adrenergic agonist. -FMH totally abolished the increase in serum corticosterone induced by carbachol, a cholinergic muscarinic receptor agonist and significantly diminished the rise in corticosterone levels induced by clonidine, an ₂-adrenergic agent. Pretreatment with the histamine receptor antagonists mepyramine and cimetidine also considerably reduced the carbachol-induced corticosterone response and the response induced by clonidine.These results indicate that brain neuronal histamine is considerably involved in stimulation of the HPA axis by cholinergic muscarinic and ₂-adrenergic agonists, but not by GABA_A and ₁- and -adrenergic agonists.     

Interaction between the central histaminergic and the muscarinic cholinergic systems

Histamine (HA) was given intracerebroventricularly (icv) to rats anaesthetized with pentobarbital. During the first minute after administration, HA alone elicited a small fall in blood pressure (BP) and a decrease in heart rate (HR), followed by a distinct increase in those parameters. Pretreatment with naloxone (Nx) in a dose of 0.1 μg icv significantly decreased the rise in BP and augmented the increase in HR. When the rats were premedicated with atropine methyl bromide (ATMB), 15 min before histamine, higher doses of ATMB (100 μg icv or 25 μg ip) significantly inhibited the histamine induced BP rise. However, a very small dose (0.1 μg) of ATMB stimulated the hypertensive response, but only after its peripheral and not central application. These changes were significantly reversed by icv pretreatment with Nx. HA-induced changes in HR, in contrast to BP, were not significantly modified by ATMB.

     

Interaction between the central histaminergic and the muscarinic cholinergic systems

Histamine (HA) was given intracerebroventricularly (icv) to rats anaesthetized with pentobarbital. During the first minute after administration, HA alone elicited a small fall in blood pressure (BP) and a decrease in heart rate (HR), followed by a distinct increase in those parameters. Pretreatment with naloxone (Nx) in a dose of 0.1 g icv significantly decreased the rise in BP and augmented the increase in HR. When the rats were premedicated with atropine methyl bromide (ATMB), 15 min before histamine, higher doses of ATMB (100 g icv or 25 g ip) significantly inhibited the histamine induced BP rise. However, a very small dose (0.1 g) of ATMB stimulated the hypertensive response, but only after its peripheral and not central application. These changes were significantly reversed by icv pretreatment with Nx. HA-induced changes in HR, in contrast to BP, were not significantly modified by ATMB.     

Involvement of the histaminergic system on appetitive learning and its interaction with haloperidol in goldfish

This study investigated the actions of the histaminergic system on appetitive learning and memory, and its interaction with the dopaminergic system in goldfish. It consisted of nine sessions, in which fish were tested in a four-arm tank. On day 1, the animals were habituated for 10 min. On day 2, they were placed in one arm and had to find food at the left or the right arm. Time to begin feeding was recorded, and the procedure repeated for more 3 days (training phase). On training day 4, seven groups were injected with saline, seven with haloperidol (2.0 mg/kg) and one with DMSO solution before training and after feeding, three groups received saline, six chlorpheniramine (CPA) (1.0, 4.0 and 8.0 mg/kg), and six l-histidine (LH) (25, 50 and 100 mg/kg). Saline groups were considered as control of CPA and LH treated groups and DMSO as control of haloperidol. A non-injected group was also included. Testing occurred after 24 h. A reversal procedure was conducted 24h after testing and repeated for 3 days. The groups receiving CPA at 1.0 and 8.0 mg/kg and LH at 25, 50 and 100 mg/kg differed between Test and Reversal day 1. Pre-treatment with haloperidol plus 8.0 mg/kg of CPA and 25 and 50 mg/kg of LH reverted the treatment effect. However, in the groups treated with 1.0 mg/kg of CPA and 100 mg/kg of LH, the difference remained. This study confirmed the interaction between the histaminergic and the dopaminergic systems on memory process in goldfish.     

The interaction of ethanol and zinc on hepatic glutathione and glutathione transferase activity in mice

The effects of ethanol and/or zinc sulphate on liver glutathione and glutathione transferase activity were studied in mice. Ethanol suppressed glutathione transferase activity and had no significant effect on glutathione levels in the organ. Zinc sulphate administration dose-dependently increased glutathione transferase activity but did not affect hepatic glutathione content. Furthermore, the depressive action of ethanol on glutathione transferase activity was prevented by zinc sulphate pretreatment. It is suggested that zinc sulphate can reactivate glutathione transferase which in turn increases the excretion of the active metabolites produced by ethanol, through conjugation with glutathione in the liver. This action of zinc may alleviate the hepatic toxicity of ethanol in mice.     

Central histaminergic H3-receptors and locomotor activity

Inflammation Research -     

Involvement of the histaminergic system in the central cardiovascular regulation in haemorrhage-shocked rats with portocaval anastomosis

Inflammation Research -     

Involvement of central histaminergic mechanisms and prostaglandins in carbachol-induced corticosterone secretion

Inflammation Research -     

Interactions between the histaminergic and angiotensinergic systems in the central cardiovascular regulation in rats

Inflammation Research - .     

Lipid lowering activity of Citri unshii pericarpium in hyperlipemic rats

The inhibitory effect of the MeOH extract of Citri unshii pericarpium (CU) and its fractions were tested in hyperlipemic rats using for animal models induced by high cholesterol-diet. We measured plasma levels of triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol as measures of its hyperlipemic effects. We demonstrated that CU decreases plasma levels of triglyceride, total cholesterol and LDL cholesterol. There was also no elevation of plasma ALT and AST levels, which indicate CU did not cause liver injury. These results indicate that CU is a good candidate for the treatment on high cholesterol diet-induced blood circulatory disorders, obesity and hyperlipidemia.     

Effect of social isolation on corticosterone secretion elicited by histaminergic stimulation

Social stress of crowding for 3, 7, 14 and 21 days drastically reduces the serum corticosterone response to intracerebroventricular administration of dimaprit, a histamine H₂-receptor agonist, moderately diminishes the response to pyridylethylamine, an H₁-receptor agonist, and does not change significantly the corticosterone response to histamine.

These results suggest that social stress of crowding considerably desensitizes central histamine H₂-receptors involved in stimulation of the hypothalamic-pituitary-adrenal axis.

     

Interactions between the histaminergic and opioidergic systems in the central cardiovascular regulation – haemodynamic studies

Inflammation Research -     

Mother-infant interaction and the modulation of pituitary-adrenal activity in rat pups after early stimulation

In Experiment I, handling or electric shock of 2-day-old rat pups triggered pituitary-adrenocortical activity. Interaction between mother and litter after pup treatment affected the magnitude and the time course of the pups' adrenocortical response. Mother-infant interactions following pup treatment on Day 2 were found to affect the responsiveness of pups to later stimulation. In Experiment II handled or shocked pups that were returned to a mother-absent nest were subsequently found to be less responsive to ACTH injection than were pups returned to a mother-present nest following treatment. These data are discussed in terms of the reciprocity and synchrony in mother-infant interactions and the Maternal Mediation hypothesis of early experience.