Hypothalamus Of Conscious Rats Research Articles

Swimming stress that causes hyperglycemia increases in vivo release of noradrenaline, but not acetylcholine, from the hypothalamus of conscious rats

The effects of acute swimming stress (10 min) on noradrenaline release from the medial basal hypothalamus (MBH; consisting of the ventromedial and dorsomedial hypothalamus) and acetylcholine release from the lateral hypothalamic area (LHA) were investigated in freely moving rats by using in vivo microdialysis techniques. Serum glucose, noradrenaline and adrenaline concentrations were also determined. Acute swimming stress produced significant hyperglycemia, with increases in serum noradrenaline and adrenaline concentrations. The release of noradrenaline from the MBH was significantly stimulated during the swimming stress. On the other hand, the swimming stress has no significant effect on the release of acetylcholine from the LHA. These findings support the idea that hypothalamic noradrenergic neurons play an important role in the sympathoadrenal hyperglycemic response to stressful stimuli. Moreover, it is suggested that hypothalamic cholinergic neurons are not involved in the responses of serum glucose, noradrenaline and adrenaline concentrations to swimming stress.

On a dual role for clonidine stimulation of the ventromedial nucleus of the hypothalamus in sodium and potassium renal excretions of rats.

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an alpha 1-adrenergic receptor antagonist) and yohimbine (an alpha 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of alpha 1-adrenoceptors and that inhibitory effects require alpha 2A-adrenoceptors.

Serotonin outflow in the hypothalamus of conscious rats: origin and possible involvement in cardiovascular control

The push-pull technique was used to investigate the effects of neuroactive compounds and experimentally induced blood pressure changes on the release of endogenous serotonin in the posterior hypothalamic area of the rat. Hypothalamic superfusion with artificial cerebrospinal fluid which contained 80 mM K + or 1 μM veratridine enhanced the rate of serotonin release. Superfusion with tetrodotoxin (5 μM) led to a pronounced decrease in the serotonin release rate. Increases in blood pressure elicited by intravenous infusions of noradrenaline (3–4 μg/kg/min) or phenylephrine (10 μg/kg/min) enhanced the release of serotonin in the hypothalamus. Similarly, the serotonin release rate was enhanced by hypervolaemia. Decreases in blood pressure elicited by intravenous administration of nitroprusside (30–40 μg/kg/min) or chlorisondamine (3 mg/kg) reduced the release of serotonin. Likewise, the serotonin release rate was decreased by hypovolaemia. With one exception (hypothalamic superfusion with tetrodotoxin) neither neuroactive drugs, nor experimentally elicited blood pressure changes modified the release rate of the metabolite 5-hydroxyindoleacetic acid (5-HIAA). These findings show that changes in blood pressure lead to counteractive alterations in the release of serotonin. Thus, serotoninergic neurons of the posterior hypothalamus seem to be involved in the homeostasis of blood pressure by exerting a hypotensive function. At least in the hypothalamus, the concentration of 5-HIAA in the superfusate does not seem to be a reliable marker for the activity of serotoninergic neurons.

Simultaneous Increases of Extracellular Monoamines in Microdialysates from Hypothalamus of Conscious Rats by Duloxetine, a Dual Serotonin and Norepinephrine Uptake Inhibitor

Simultaneous Increases of Extracellular Monoamines in Microdialysates from Hypothalamus of Conscious Rats by Duloxetine, a Dual Serotonin and Norepinephrine Uptake Inhibitor

Simultaneous increases of extracellular monoamines in microdialysates from hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine uptake inhibitor.

Duloxetine (LY248686, [+]-N-methyl-3-(1-napthalenyloxy)-2-thiophene-propanamine) is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) uptake in hypothalamus and cerebral cortex of rat brain (Wong et al. 1993; Fuller et al. 1994). Consistent with the dual mechanisms of inhibiting 5-HT and NE uptake, duloxetine at 15 mg/kg IP produced large increases in extracellular levels of 5-HT (250%) and NE (1,100%) 30 minutes after systemic administration. Levels of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), metabolites of NE and 5-HT, respectively, were reduced, whereas those of dopamine (DA) and its metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Duloxetine at 7 mg/kg produced less pronounced increases while no consistent effects were observed at 4 mg/kg. In this dose range, duloxetine inhibited 5-HT uptake in platelets ex vivo without inhibiting striatal dopamine (DA) uptake. In the present study we also found that the primary amine (a racemate) of duloxetine is about one-fourth as active as duloxetine to inhibit 5-HT and NE uptake. The potential primary amine metabolite of duloxetine might contribute, in part, to the inhibition of 5-HT and NE uptake in vivo. Thus the ability to produce robust increases of extracellular 5-HT and NE levels suggests that duloxetine may potentially be a highly effective antidepressant agent.

Effect of intrahypothalamic insulin on sympathetic nervous function in rats drinking a high-sucrose solution

Hyperinsulinemia has been associated with increased sympathetic nervous activity. However, direct injection of insulin into the hypothalamus of anesthetized rats produces sympatho-inhibition. This discrepancy could be due to confounding effects of anesthesia or insulin resistance on central neural function. The effect of injecting saline or insulin (3.0 or 30 mU) into the ventromedial hypothalamus on mean arterial pressure, heart rate, and renal nerve activity (RNA) was investigated in conscious rats and in rats anesthetized with urethan or pentobarbital. Insulin decreased RNA in conscious rats but had no effect in pentobarbital-anesthetized rats. In urethan-anesthetized rats with hyperglycemia, the insulin increased RNA. Drinking a 10% sucrose solution enhanced the sympathoexcitatory effect of insulin in the urethan-anesthetized rats but had no effect in the other two groups. The sucrose solution did not affect insulin sensitivity in any group; however, urethan anesthesia did produce insulin resistance. These data show that central effects of insulin are sensitive to anesthesia and do not support a sympathoexcitatory role for insulin in the ventromedial hypothalamus of conscious rats, at least in relation to the renal sympathetic nerves.

Pulsatile release of histamine in the hypothalamus of conscious rats

The pattern of histamine release was investigated in the hypothalamus of the conscious, freely moving rat over 20 h. Under anaesthesia, a guide cannula was stereotaxically inserted into the posterior hypothalamus. In the conscious animal, the stylet of the guide cannula was replaced by a push-pull cannula, and the hypothalamus was superfused with artificial cerebrospinal fluid. Histamine was determined radioenzymatically in the superfusate which was continuously collected in time periods of 20 min. The release rate of histamine fluctuated according to an ultradian rhythm (frequency: 1 cycle per 83 min) and a circadian rhythm with the highest release rate of histamine between 11.00 p.m. and 1.00 a.m. The release rate of histamine during darkness was higher than that during the light period. The results demonstrate that, in the brain, neuronal histamine is released according to rhythms with various frequencies.

Absence of neural responses following suppression of the immune response by cyclophosphamide

Injection of sheep red blood cells (SRBC) as an antigenic stimulus, causes significant increases (up to 300%) in multiunit neural activity in the preoptic area/anterior hypothalamus of conscious rats. This increase occurs on the fifth or sixth day after immunization, at the time of first appearance of circulating antibodies at a serum titer of 1:32, increasing to 1:128 by day 10 following sensitization. Treatment with the immunosuppressive drug cyclophoshamide was able to prevent both antibody production and the expected increases in electrical activity in 5 of 6 rats; the one remaining animal showed a low level of circulating anti-SRBC antibodies on day 10 (1:32) and also, a small increase (36%) in neural activity at the expected time. These results provide further evidence that activation of the immune system is able to alter neuronal activity in an area of the brain important in the regulation of both neuroendocrine and neuroimmunomodulatory mechanisms, and that such activity is probably due to soluble secretory products released from components of the immune system.

Direct evidence of conditioned fear-elicited enhancement of noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis

Inescapable footshock stress produced marked increases in noradrenaline (NA) release, which was assessed by intracranial microdialysis, in the hypothalamus of conscious rats. Emotional stress, without physical stimuli (replacement to the environment where the rats had received footshock previously), also increased hypothalamic NA release. These results suggest that foodshock stress caused increases in NA release and this activation of NA neurons appears to be reinstated simply by re-exposure to the environment previously associated with shock.

Factors causing natriuresis after hypothalamic injection of a cholinergic drug in rats.

We investigated possible mechanisms for the natriuresis seen after injection of the cholinergic drug carbamylcholine chloride (carbachol) into the lateral hypothalamus of conscious rats. In unrestrained rats injection of 1 microgram of carbachol in 1 microliter of 0.15 M NaCl solution through a permanently implanted cannula produced a significant natriuresis and kaliuresis. Injection of vehicle produced no changes. The same animals were then subjected to bilateral renal denervation (n = 13) or sham denervation (n = 13) and injected with the same solutions 1 wk later. Carbachol injection produced a natriuresis (P less than 0.0001) and a kaliuresis (P less than 0.01) in all animals studied. Both responses were of a magnitude similar to the responses seen before denervation. We studied other rats while awake but restrained, which permitted the performance of clearance studies and blood pressure measurements. Injection of carbachol produced diuresis, natriuresis, and kaliuresis in all rats, with no change in p-aminohippurate clearance and only transient change in inulin clearance. An increase in blood pressure occurred in some but not all rats. The response in rats with bilaterally denervated kidneys (n = 7) was similar to that of rats with innervated kidneys (n = 5). The natriuresis seen after cholinergic stimulation of the hypothalamus in conscious rats is not primarily mediated by inhibition of renal nerve activity and can be dissociated from changes in blood pressure, glomerular filtration rate, and renal plasma flow.