Brain histamine-plasma corticosterone interactions.

Significant elevation in plasma corticosterone of rats achieved by intraperitoneal (i.p.) administration of corticosterone (2.4 mg/kg) was associated with a rapid (2.5 min) and significant increase in hypothalamic histamine (HA) levels which persisted for 60 min. Midbrain and cortical HA concentrations were not affected. Significant and prolonged elevation of hypothalamic, midbrain and cortical HA levels was achieved by L-histidine administration (500 mg/kg i.p.). The most significant increase was noted in the hypothalamus and persisted for 10 hours. The elevated brain HA levels were associated with significant increase in plasma corticosterone levels which lasted for 120 mins. Present data supports the involvement of central HA in endocrine function.

Brain histamine response to stress in 12 month old rats.

The regional brain histamine regulation in response to stress was investigated in 12 month old Sprague-Dawley male rats. Air blast exposure (15 min) induced significant (26.5%) elevation in hypothalamic HA level; midbrain and cortical HA concentrations were not affected. Histamine methyltransferase activity was not altered by stress in any of the brain regions investigated. Plasma corticosterone levels of stressed rats were significantly elevated (6.5 fold). Hence, the response of hypothalamic HA to stress is still evident in 12 month old rats.

Single and repeated air blast stress and brain histamine.

Exposure of rats to air blasts for 1, 5 and 15 min resulted in a significant increase in plasma corticosterone level and in the hypothalamic histamine concentration. Midbrain histamine content was increased after 1 and 5 min of exposure but cortical histamine increased following 1 min of exposure only. Stress of longer duration (30 mins did not significantly affect histamine concentration in any of the three brain regions investigated, although plasma corticosterone level remained very significantly (14.5-fold) elevated. Repeated exposure of rats to air blasts of 15 min duration resulted in a significant elevation of hypothalamic histamine concentration while midbrain and cortical histamine was not significantly altered. Plasma corticosterone level was again very significantly (10-fold) increased. Present results suggest the involvement of brain histamine in the response to stress.

Effect of diazepam on stress induced changes in brain histamine.

Acute treatment with diazepam (2.5, 5 and 10 mg/kg) did not affect the basal histamine concentration in the hypothalamus, midbrain or in the cortex of the rat. The increase in the hypothalamic histamine level caused by 15 min of "platform stress" was significantly attenuated by diazepam (5 or 10 mg/kg) pretreatment, but the elevation induced by 15 min of air blasts remained unchanged. Diazepam significantly reduced the rise in plasma corticosterone concentration in response to air blast stress but did not affect the increase caused by "platform stress." Thus, in addition to the already known effects of diazepam on stress induced changes in other central neurotransmitters or neuromodulators, diazepam may also affect the hypothalamic histamine elevation induced by certain type of stress.

Brain histamine regulation following chronic diazepam treatment and stress.

Chronic diazepam treatment (5 mg/kg intragastrically, twice daily for 14 days) did not influence either hypothalamic, midbrain or cortical histamine (HA) levels or histidine decarboxylase (HD) activity in male Sprague-Dawley (200-220 g) rats. However, a small but significant decrease in hypothalamic HA concentration and significantly increased HD activity was seen following diazepam withdrawal. Air blast stress induced a significant elevation in hypothalamic HA levels and HD activity in vehicle-treated controls, diazepam-treated and diazepam-withdrawn rats, but the change in HD activity was significantly greater in the last group. The latter group also displayed the greatest elevation in plasma corticosterone levels in response to stress. Hence, diazepam withdrawal in rats results in some changes in the basal hypothalamic HA regulation and may influence the hypothalamic HA and corticosterone response to stress.

Effect of stress on brain histamine.

Stress of short duration (5 min) resulted in a significant increase in plasma corticosterone level and a significant decrease in the midbrain histamine concentration in rats. Exposure to 15 min stress caused a significant elevation in the hypothalamic histamine level. Stress of longer duration (30 or 60 min) did not affect hypothalamic, cortical or midbrain histamine concentration although plasma corticosterone level remained elevated. Repeated exposures of rats of 15 min stress did not significantly alter histamine concentration of any of the brain regions studied. Plasma corticosterone concentration was only 28% of that observed in animals exposed to single 15 min stress. Present data suggest a role of brain histamine in response to stress.

Effect of diphenhydramine on stress-induced changes in brain histidine decarboxylase activity, histamine and plasma corticosterone levels.

Exposure of rats to platform stress induced a significant elevation in hypothalamic histamine levels. Air blast-stress resulted in a significant increase in hypothalamic histamine concentration and in histidine decarboxylase activity. No significant changes were noted either in the enzyme activity or in histamine levels in the midbrain or cortex of stressed rats. In the nonstressed rats, diphenhydramine (7.5 mg/kg intragastrically), a H1-receptor antagonist, did not influence histidine decarboxylase activity or histamine concentration in any of the three brain regions investigated. However, diphenhydramine pretreatment prevented the increase in histidine decarboxylase activity induced by air blasts. In untreated rats, plasma corticosterone levels were significantly elevated following either platform stress (4.5-fold) or air blasts (7.8-fold). A significant increase was also noted in saline and diphenhydramine-treated animals following these stressors, however, the increase in saline or diphenhydramine treated rats following air blasts was significantly less than that seen in untreated stressed controls.

Brain histamine: plasma corticosterone spontaneous locomotor activity and temperature.

Hypothalamic histamine exhibited circadian fluctuations in male Sprague-Dawley rats; low values were found during the dark period when spontaneous locomotor activity (S.L.A.) and temperature were elevated. A relatively high hypothalamic histamine level was observed during the early period of the light cycle and was associated with decreased S.L.A. and temperature. Histamine concentration was high when corticosterone levels were low at the end of the dark cycle and during the morning hours (4 a.m.-1 p.m.); but histamine levels were relatively constant while corticosterone concentration dropped during afternoon and early night hours (4 p.m.-10 p.m.). Furthermore, the lowest hypothalamic histamine level (at 1 a.m.) was associated with the average plasma corticosterone value, thus no consistent relationship between histamine and corticosterone levels could be observed. Circadian fluctuations in brain histamine may support its role in brain function.

Tyrosine hydroxylase activity in rat brain regions after chronic treatment with +/--propranolol.

Rats were injected twice daily with +/--propranolol (6 mg kg-1 day-1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum.

Possible role of histamine in brain function: neurochemical, physiological, and pharmacological indications.

Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine.

Changes in the regional brain histamine and histidine levels in postmortem brains of Alzheimer patients.

In postmortem brains of Alzheimer patients, statistically significant decreases in histamine levels were observed in the frontal (45%), temporal (20%), and occipital cortices (38%) and in the caudate nucleus (25%). Histidine levels were decreased in the frontal (15%), temporal (21%), and occipital cortices (30%) and in the caudate nucleus (25%); the decrease was statistically significant in the last two brain regions. Histamine was determined by the double isotope technique, and histidine was determined fluorometrically by a fluorescamine method. The data indicate that brain histamine regulation is altered in Alzheimer's disease.

Age-related changes in brain histamine.

The effect of age on brain histamine levels and histamine methyltransferase activity (HMT) was investigated. Male Sprague-Dawley rats (12 months old) displayed significantly higher hypothalamic, midbrain and cortical histamine concentrations than three-month-old animals. In contrast, HMT activity was significantly decreased in all three brain regions. The increase in brain histamine concentration of old rats could have been partially attributed to decreased activity of HMT since elevated levels of brain histamine are known to occur following HMT inhibition. Present results indicate that similarly to the reported changes in the concentration, synthesis and/or metabolism of other central neurotransmitters in old rats, brain histamine regulation may also be affected in the process of aging.

Effect of histidine on morphine-induced changes in brain histamine.

Chronic morphine administration to rats resulted in a significant decrease in the hypothalamic and cerebro-cortical histamine concentrations. These low histamine values were restored to control levels when L-histidine was administered daily along with morphine treatment. Chronic treatment with L-histidine prevented the midbrain and cerebro-cortical histamine depletion in morphine-withdrawn rats, whereas in the hypothalamus the histamine level remained significantly decreased. The present data suggests that histamine may play a role in morphine dependence and withdrawal.