Summary1. In cats anaesthetized with intravenous chloralose, microinjections of tubocurarine, leptazol, strychnine or picrotoxin, in a volume of 1 ,lt, were made into the grey matter of the cerebral cortex and the electrical activity was recorded from the site of injection with the microinjection cannula which, insulated except at its tip, served as recording electrode. 2. Routinely the injections were made into the gyrus splenialis or into the underlying gyrus cinguli close to the mid-line, because the injections would then most likely be in grey and not in white matter. Injected in this way all four drugs set up foci of excitation which gave rise to synchronous firing of a large number of neurones with the result that high voltage negative spikes were recorded from the microinjection cannula. 3. On injection into the gyrus splenialis the threshold dose was about 0-04 ,ug for picrotoxin, about 0 2 ,ug for tubocurarine, about 5 ,tg for strychnine and 25 to 50 1tg for leptazol. Following the injection of larger doses the spike discharge continued for a few hours after picrotoxin and tubocurarine, for over an hour after strychnine, but for a few minutes only after leptazol. On injection into the gyrus cinguli the threshold doses were slightly greater and with larger doses the spikes occurred at greater frequency but were of lower voltage than in the gyrus splenialis. 4. With large doses of picrotoxin injected into the gyrus splenialis the spikes developed an after-positivity and an after-discharge which sometimes passed into a short period of fast activity. 5. The foci of excitation set up by the drugs were restricted to the site of injection because on raising or lowering the microinjection cannula the spikes recorded from it quickly decreased in voltage and then disappeared. When the injections were made close to a sulcus and the microinjection cannula, on being lowered, traversed the sulcus, the spikes changed their polarity. 6. The spike discharge appears to be a consistent response to the injections of the drugs into grey matter of any part of the cerebral cortex since it was also obtained on their injection into the pyriform cortex, amygdala and area retro-
It was recently shown that morphine, like 5-hydroxytryptamine (5-HT), produces hypothermia in rats, but hyperthermia in cats, when acting on the anterior hypothalamus (Lotti, Lomax & George, 1965; Banerjee, Feldberg & Lotti, 1968). Because morphine depletes the monoamines of the brain the possibility has been discussed that 5-HT may be the mediator of its temperature effects in these species. In the present experiments morphine was injected into the cerebral ventricles of rabbits to see if in this species, too, its effect on temperature resembles that of 5-HT similarly applied.In the course of the experiments, an effect of morphine was obtained which so far seems to have been observed with this alkaloid in rats only (Reynolds & Randall, 1957)-that is, catalepsy. It developed not only when the morphine was given by the intraventricular route but also following its injection into the cisterna magna. METHODSNew Zealand white or Dutch rabbits of both sexes weighing 1.7-3 kg were used. A Collison cannula was aseptically implanted under pentobarbitone sodium anaesthesia into the left lateral cerebral ventricle. The point of insertion was 7 mm lateral to the midpoint of the sagittal suture as described by Hasselblatt & Sproull (1961). An interval of at least 3 days was allowed between implantation of the cannula and the injection of drugs. They were injected in a volume of 0.1 ml. followed by 0.05 ml. of 0.9% NaCl solution.For injections into the cisterna magna the rabbit was restrained by hand, the neck was flexed and a 23 gauge needle with stilette was pushed through the skin and muscle in the midline just posterior to the lower margin of the occipital bone until the tip of the needle was felt to penetrate the dura. If the tip had entered the cisterna, clear cerebrospinal fluid (c.s.f.) welled up in the hub of the needle when the stilette was removed. A 1 ml. glass syringe filled with either 0.9% NaCl or the morphine solution was then attached to the needle and a volume of 0.1 ml. fluid was allowed to flow in by gravity. If no c.s.f. appeared in the needle hub or if the fluid was tinged with blood, no injections were made. Little discomfort seemed to be caused either by insertion of the needle or by the injection, for the rabbit made no attempt to struggle.In order to see which areas of the brain are reached by solutions injected in this way, 0.1 ml. of a 0.2% solution of bromophenol blue, prepared as described by Feldberg & Fleischhauer (1960a), was injected into the cisterna magna of unanaesthetized rabbits. Within a few minutes this produced vigorous scratching movements which result from an action on structures near the dorso-lateral surface of the upper cervical cord, because bromophenol blue applied to this region is known to
Morphine and ergotamine have been examined in cats to find out how they affect body temperature when acting on the hypothalamus. The two substances were chosen to investigate whether a substance such as morphine, which reduces the monoamines in the hypothalamus, affects body temperature when injected into the cerebral ventricles, and whether a substance such as ergotamine, which blocks the action of the monoamines in peripheral tissues, exerts this effect also on the anterior hypothalamus.
SUMMARY1. In unanaesthetized rabbits and cats reserpine was injected through a chronically implanted cannula in the left lateral cerebral ventricle, and rectal temperature was recorded.2. In rabbits the reserpine (0-5-0.6 mg) caused a rise in temperature, frequent defaecation and sedation. On repeating the intraventricular injections at 24 hr intervals the rise in temperature was not obtained with the second or third injection, but defaecation and sedation still occurred. When the hyperthermic response to intraventricular reserpine had disappeared the anterior hypothalamus still responded to intraventricular noradrenaline which produced a rise in temperature.3. In cats the reserpine (0.5-0.75 mg) caused a biphasic change in temperature, i.e. an initial fall followed by a rise, frequent defaecation, and catalepsy. On repeating the intraventricular injections at 24 hr intervals the initial hypothermic phase of the temperature response was not obtained with the second or third injection, but the late rise, defaecation and catalepsy were still produced. When the hypothermic phase had disappeared the hypothalamus still responded to intraventricular noradrenaline or adrenaline which produced a fall, and to intraventricular 5-hydroxytryptamine (5-HT) which produced a rise in temperature.4. It is concluded that the rise in temperature in rabbits and the initial fall produced in cats is not due to a direct action of reserpine on the cells of the anterior hypothalamus but to noradrenaline released from adrenergic
SUMMARY1. In unanaesthetized cats the effect on rectal temperature was examined of 5-HT injected through a Collison cannula chronically implanted into the left lateral ventricle. The response depended on the amount of 5-HT injected and on the solvent employed.2. An intraventricular injection of 200 ,ug 5-HT creatinine sulphate dissolved in 0 9 % NaCl solution resulted in a long-lasting rise often interrupted initially by a transient fall in temperature.3. This fall became more prominent with larger doses of 5-HT; even more when the 5-HT was dissolved in distilled water, and then the hyperthermic effect was attenuated.4. It is concluded that intraventricular 5-HT raises rectal temperature in cats when the amount is not too large, and that a hypothermic effect when it occurs results from paralysis of cells in the anterior hypothalamus which are excited by small doses. This would be similar to the actions of acetylcholine in the perfused superior cervical ganglion of the cat, where small doses excite but large doses paralyse the ganglion cells.5. An intraventricular injection of distilled water produced a steady rise in temperature which is attributed to release of 5-HT.
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