Regional metabolism of 5-hydroxytryptamine in brain under acute and chronic heat stress.

The metabolic alteration of 5-HT in four different regions of rat brain and plasma was studied under acute and chronic heat stress. A generalised elevation of 5-HT in all the brain regions along with high plasma level was observed in animals subjected to 4 hour heat stress at 38 degrees C. Such elevation of brain 5-HT may be due to entry of plasma 5-HT into the brain owing to breakdown of blood-brain barrier (BBB). In heat adapted rats, where BBB remained unaffected, no increase in brain 5-HT was observed, rather a significantly low level was maintained both in plasma and brain tissue.

Involvement of histamine receptors in mediation of histamine induced thermoregulatory response in rats.

At there ambient air temperature range, the rectal temperature changes following infusion of histamine either into lateral ventricle (L.V.) or IVth ventricle (IVth V) were studied. At an ambient temperature range of 19-22 degrees C, hypothermia occurred following histamine infusion either into L.V. or IVth V. Hypothermia elicited from infusion of histamine into L.V. was prevented with pretreatment of H1-receptor blocker (mepyramine), but in case of IVth V, it was prevented with H2-receptor blocker(cimetidine). These H1 and H2-receptor antagonists were ineffective in preventing hypothermia following histamine infusion into either L.V. or IVth V, when the ambient air temperature was maintained low (11-13 degrees C).

Thermoregulatory response in rats following administration of histamine in different CSF compartments.

Recently histamine is being considered as an important neurotransmitter/neuromodulator in the central nervous system. This has been supported from the present observations with regard to thermoregulatory responses elicited following histamine administration into different CSF compartments. Administration of histamine into the right lateral cerebral ventricle of rats showed a dose dependent fall in rectal temperature. This hypothermic response was evident only at moderately low or at thermoneutral ambient temperature. Administration of histamine into fourth ventricle produced hypothermic response at low ambient temperature and hyperthermia at thermoneutral ambient temperature, which was no longer observed when the ambient temperature remained above the thermoneutral zone. Infusion of histamine into spinal subarachnoid space produced hyperthermia which developed very slowly. However, the infusion of histamine into the subarachnoid space around the brain stem did not exhibit any change in rectal temperature. The significance of these observations has been discussed.

Effect of graded distension of urinary bladder on arterial blood pressure and neurohumors in rabbits.

Effect of graded distension of urinary bladder has been observed on the circulating level of catecholamine, cortisol and serotonin along with arterial blood pressure in rabbits. Simultaneously adrenal catecholamine has been also investigated. Similar pattern of increase has been observed in the levels of catecholamine, cortisol, serotonin and arterial blood pressure after bladder distension at 20 ml, 40 ml and 60 ml volumes. On this basis, it may be inferred that there is some role of the vasoconstrictor humors released during bladder distension in pressor response. At the same time, decrease in adrenal catecholamine level also supports this.

Role of 5-HT on increased permeability of blood-brain barrier under heat stress.

Exposure of young rats (9-10 wks) to chronic summer heat (36 degrees C) or acute heat (38 degrees C 4hr) increased the BBB permeability to Evans blue albumin complex (MW 68,000) and 131I-sodium (MW 154) in different brain regions which correlated well with the increased level of 5-HT in plasma and brain. This increased permeability of BBB and the increased 5-HT level were prevented by pretreatment with p-CPA, indomethacin and diazepam. Cyproheptadine and vinblastine pretreatment however, prevented only the increased permeability of BBB, the plasma and brain 5-HT level continued to remain high. These results indicate a probable role of 5-HT as one of the factors leading to the increased permeability of BBB in young rats following heat stress.

Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats.

The progression and persistence of oedema development following impact-injury on closed skull was studied in anaesthetised as well as in unanaesthetised rats. The degree and rate of oedema development, following trauma, was aggravated in anaesthetised hypothermic animals but was reduced/or delayed by maintenance of body temperature at euthermic level. In general, the unanaesthetised animals showed a greater accumulation of oedema fluid than the corresponding anaesthetised group. The development of oedema corresponded more or less with the accumulation of 5-HT level in plasma and brain. This development of oedema was completely prevented following pretreatment with p-CPA, indomethacin paracetamol and aminophylline in unanaesthetised animals; whereas these drugs were able only to partially reduce the oedema development in euthermic anaesthetised animals. On the other hand the cyproheptadine pretreatment aggravated the oedema development which was more pronounced in unanaesthetised animals. The probable mechanism of the action of these drugs has been discussed.

Effect of voluntary retention of urine on plasma and urinary biogenic amines as well as circulatory and respiratory responses.

Stress caused by voluntary retention of urine in 25 normal healthy volunteers has been estimated by measuring the levels of biogenic amines (serotonin, catecholamine) in blood and urine. Estimations were done before and after voluntary retention of urine. Plasma and urine catecholamines and 5-HT significantly increased after retention. Simultaneously rise in BP, PR, RR were also observed. Inference has been drawn that retention of urine may induce stress.

Anterior cerebellum as a site for morphine analgesia and post-stimulation analgesia.

The microinjection of 10 micrograms Morphine into culmen region of anterior cerebellum produced profound analgesia in rats, and this was antagonised with intraperitoneal administration of naloxone. On the other hand, the same injection of morphine into lobus simplex and declive region of posterior cerebellum was without any effect on nociception. Further it was observed that chronic surgical ablation of culmen-centralis region of anterior cerebellum markedly diminished the duration of analgesia elicited with systemic administration of morphine, though ablation per se had no influence on nociception. Also, the focal electrical stimulation of culmen region for brief period exhibited post-stimulation analgesia. These findings indicate that anterior cerebellum specifically plays some role in the modulation of physiological mechanisms of pain relief.

Morphine hyperthermia in rats: role of neurochemical substances in brain.

Central neurochemical mechanism underlying the hyperthermic effect of morphine has been investigated in rats. 200 micrograms morphine hydrochloride, when administered through cerebroventricular route at different seasonal air temperature, caused a rise in rectal temperature of rats. This hyperthermia was not affected by prior administration of antiserotonergic (pCPA, 5.6-DHT) or anticatecholaminergic (PBZ, 6-OHDA) drugs, as well as by PGE synthetase inhibitor, indomethacin. Similarity, cholinergic muscarinic or nicotinic receptor blockers, such as atropine and pentolinium/ D-tubocurarine respectively, were ineffective to modify it. Whereas, the depletion of acetylcholine in brain by pretreating the animals with hemicholinium profoundly delayed the hyperthermia, suggesting a central cholinergic involvement in morphine induced hyperthermia in rats.

Impairment of blood-brain barrier (BBB) in rat by immobilization stress: role of serotonin (5-HT).

Influence of immobilization stress on blood-brain barrier (BBB) was studied in rats using Evans blue as barrier tracer. 7-9 hr of of immobilization had increased the permeability of BBB mainly in younger rats. This increased permeability was significantly reduced with p-CPA, indomethacin or vinblastine pretreatment. Theophylline treatment caused early extravasation of Evans blue dye. The increased level of serotonin in immobilization and infusion of 5-HT in model experiments suggest a causative role of serotonin in the increased permeability of BBB induced by immobilization stress.

Studies on rectal temperature of rats in relation to seasonal air temperature and morphine administration.

The present findings demonstrate that seasonal air temperature does not only influence the basal core temperature of rats, but also modifies the physiological/pharmacological actions of drugs. Thus, at low ambient temperature, intracerebroventricular on intraperitoneal administration of morphine produces mainly hypothermia followed by a secondary rise in rectal temperature. On the other hand, at high ambient temperature, the drug produces hyperthermia only. The hypothermic response at low ambient temperature is abolished by pretreatment of rats with 6-hydroxydopamine but not with phenoxybenzamine administration. This suggests that catecholamine pathway in the central nervous system is involved in morphine induced hypothermic response. Further, the role of cholinergic neurons in such response is also indicated.

Cerebral oedema and blood-brain and blood-CSF barriers in experimental brain trauma: effect of indomethacin-A prostaglandin synthetase inhibitor.

Cerebral oedema often occurs following trauma to the brain. Recently several biogenic amines have been suggested for their possible mediation in the pathophysiology of traumatic brain oedema. The present investigation indirectly indicates that prostaglandins of E series are also involved in the etiology of cerebral oedema, since administration of a potent PG synthetase inhibitor, indomethacin significantly diminished oedematous swelling of traumatised rat brain.

Effect of indomethacin (a prostaglandin synthetase inhibitor) on the permeability of blood-brain and blood-CSF barriers in rat.

Effect of indomethacin on the permeability of blood-brain and blood-csf barriers to Evans blue, bromophenol blue and horseradish peroxidase (HRP) was studied by administering the drug through right internal carotid artery, right external jugular vein and through intraperitoneal route in rats. Increased permeability was observed on internal carotid arterial injection but not following jugular vein or intraperitoneal injection. This increased permeability of blood-brain and blood-csf barriers following injection of indomethacin into the internal carotid artery is associated with a steep and sustained rise in mean arterial blood pressure (MABP), a feature not observed in bilateral adrenalectromised animals.

Visceral reflex responses following right intra-atrial injection of phenyldiguanide in rats.

1. Intra-atrial injection (right atrium) of pdg in nembutal anaesthetised rats produced bradycardia, hypotension and apnoea followed by hyperpnoea. In very lightly anaesthetised rats, injection of pdg close to the aortic valves produced similar responses and those responses disappeared on maintaining the animals in well-anaesthetised condition. 2. Administration of pdg either into the cerebral circulation or into cerebral ventricles did not produce bradycardia and apnoea. 3. The afferent pathway for these autonomic responses runs in vagus nerve, as shown by experiments before and after bilateral vagotomy. 4. The electrical activity of both expiratory and inspiratory muscles was inhibited during end-expiratory apnoea phase following injection of pdg into the right atrium. 5. Glycine, administered centrally or intravenously, exhibited blockade of pdg induced autonomic responses for more than forty minutes.