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1. Intraventricular clonidine and BAY 1470, administered in small doses to conscious renal hypertensive cats, produced a fall in mean blood pressure lasting for a period of 3 h. This fall in blood pressure was accompanied by a marked bradycardia. 2. Pretreatment with intraventricular phentolamine (0.3–6 μmol), piperoxan (0.18–0.74 μmol) or tolazoline (0.35–1 μmol) abolished the hypotensive effects of intraventricular clonidine (74 nmol), whereas pretreatment with haloperidol (2.6 μmol/kg, intraperitoneally), or desmethylimipramine (3.3 μmol/kg, intraperitoneally, or 1.7 μmol, intraventricularly) did not modify the cardiovascular responses to clonidine. 3. Emesis was observed 1 min after intraventricular administration of clonidine (18–112 nmol) or BAY 1470 (0.07–0.14 μmol), which always preceded the cardiovascular actions and was still observed after pretreatment with haloperidol, desmethylimipramine, phentolamine, piperoxan or tolazoline. 4. In conscious hypertensive rats clonidine (0.6 μmol/kg, intraperitoneally) produced a marked fall in blood pressure that was antagonized by centrally acting α-adrenoreceptor blocking agents but not modified by pretreatment with either 6-hydroxydopamine (three doses of 1 μmol, intraventricularly) or 5,6-dihydroxytryptamine (0.1 μmol). 5. It is concluded that the anti-hypertensive responses to clonidine are mediated via stimulation of central α-adrenoreceptors and are independent of central dopaminergic receptors, intact central serotonergic neurons and intact adrenergic uptake mechanisms.

The vasomotor and cardiac effects of gamma-aminobutyric acid (GABA) administered by different routes were studied in cats and dogs. The cat was resistant to the action of GABA administered intravenously or into a vertebral artery. Intrathecal injection of GABA into the cat depressed the vasomotor reponse to spinal compression. In dogs, intravenous, intrathecal or intraventricular injection, or topical application of GABA to the floor of 4th ventricle consistently produced hypotension and depressed the reflex and direct excitability of the vasomotor neurones, located at the supraspinal and spinal levels. Bradycardia observed after intravenous and intraventricular injections of GABA into dogs was abolished by stellate ganglionectomy but not by vagotomy. It has been attributed to depression of the central sympathetic neurones.

The cardiovascular effects resulting from intraventricular injections of 600 μg picrotoxin (a brain stem noradrenaline releasing agent) were studied in vagotomized cats previously injected intraventricularly with phenoxybenzamine (2 mg) or dichloroisoproterenol (2 mg), and compared with untreated animals. Intraventricular injections of picrotoxin always induced marked pressor responses associated with electrocardiographic changes as ventricular extrasystoles, ST-T segment deviations and tachycardia. After phenoxybenzamine, picrotoxin induced smaller (but insignificantly different) pressor responses; no ventricular extrasystoles, as well as noticeably reduced degrees of ST-T segment deviations; and a significantly greater degree of cardioacceleration. Following dichloroisoproterenol, picrotoxin induced pressor responses associated with ventricular extrasystoles and ST-T segment deviations similar to those observed in untreated animals, but a significantly smaller degree of cardioacceleration. The results are discussed, and lead to the suggestion that central sympathetic brain areas have receptors similar to those postulated by ahlquist (1948) for peripheral adrenergic receptors.

A study has been made of the effects on the rabbit electroencephalogram of injecting substances known to activate the release of pituitary antidiuretic hormone. Intracarotid injections of hypertonic saline and hypertonic glucose induced a characteristic change in the EEG of various regions of the telencephalon and diencephalon lasting approximately 20 sec. Isotonic saline and hypertonic urea served as control solutions. Hypertonic solutions were ineffective when injected into the external carotid artery. Intraventricular injections of hypertonic saline induced arousal or seizures but no EEG changes comparable to those stimulated by intracarotid injections. Repeated intracarotid injections of hypertonic saline eventually caused, in more than half of the animals, seizures which always started in the amygdala and/or hippocampus and often remained localized there.

Injections of 20 to 30 mug. of 48/80 into the cerebral ventricular spaces of mice produced a condition of motor excitement termed "delirium ambulatorium." This condition was aggravated by previous intraperitoneal injection of tranquillizers, atropine, and promethazine, not affected by previous injection of mepyramine and abolished by a previous injection of pentobarbitone. When an intraperitoneal injection of strychnine was followed by an intraventricular injection of 48/80, the strychnine convulsions became more violent, but the pattern of delirium ambulatorium was not produced.

The possible sensitivity changes caused by morphine tolerance in the postsynaptic receptors of putative neurotransmitters involved in the central thermoregulatory mechanisms were studied by intraventricular brain injections of 5-HT, NA, DA, ACh, physostigmine, pilocarpine and carbachol into 20-day old morphine-tolerant and control rats. Temperature acclimation effects were ruled out by keeping the animals in a thermoneutral environment (32°C) during the periods in which morphine would ordinarily have caused hypothermia at lower environmental temperatures. At 22–24°C, the hypothermia produced by ACh, physostigmine and both in combination was significantly greater in morphine-tolerant animals, while there were no significant differences between tolerant and control animals in the colonic temperature responses to the other substances tested. It is suggested that cholinergic receptors of pronounced ACh specificity are induced in the central thermoregulatory neurones of immature rats by repeated administration of morphine for 6 days.

CUSHING1 in 1932 injected 1 c.c. of ‘surgical pituitrin’ into the lateral ventricles of the brain of alert persons with brain tumour and noted peripheral vasodilatation, profuse sweating, salivation, fall in body temperature and a lowered basal metabolic rate. He postulated a parasympathetic region in or near the wall of the third ventricle which was activated by pituitrin. The results were criticized because of possible impurities in ‘surgical pituitrin’. In this report drug injections were made into the left lateral ventricle of the brain of the cat using surgical pituitrin (Parke-Davis), synthetic polypeptides of the posterior pituitary (PLV-2 vasopressin, and oxytocin, ‘Syntocinon’, Sandoz), synthetic angiotensin (‘Hyper-tensin’, Ciba), epinephrine, norepinephrine, the monamine oxidase inhibitors tranylcypromin (‘SKF’, Smith, Kline and French), and iproniazid (‘Marsilid’).

Patterns of reaction were studied in cats following the intraventricular (brain) injection of the venoms of Crotalus adamanteus, C. atrox, C. horridus, Agkistrodon piscivorous, A. contortrix, Centruroides sculpturatus, Vejovis spinigerus, Latrodectus mactans , and Urolophus halleri . While certain common signs were elicited, considerable variation in patterns was seen and was attributed to the direct action of the toxins on the central nervous system. Intraventricular injection of C. adamanteus venom failed to produce the typical cardiovascular responses observed following intravenous injection of Crotalus venom, indicating that the cerebrospinal fluid-blood-brain barrier relationship was not altered to any great extent by this venom. The Crotalus venoms produced changes in behavior, and motor and parasympathetic dysfunction; these were most marked following injection of C. adamanteus venom. A. piscivorus venom produced changes similar but less severe than those elicited by C. adamanteus venom. A. contortrix venom caused marked behavioral changes but relatively mild motor and parasympathetic dysfunction. The venoms of the scorpions produced severe motor, parasympathetic, behavioral, and respiratory changes. L. mactans venom stimulated parasympathetic function. U. halleri venom produced only minor and usually transient changes.

Feldberg and Sherwood's* previous studies of the behavior of cats after the intraventricular injection of various drugs opened up a new method of investigation. By this technique they showed that drugs injected into this area of high pharmacologic sensitivity could evoke various complex behavioral responses and conditions resembling sleep, anesthesia, profound muscular weakness, catatonia, and convulsions. Their classification of the effects characterized by certain common features of reaction suggested further experiments in which, in addition to the effects of the drug alone, antagonisms of various chemicals within the central nervous system might be studied. Of particular interest to experimental psychiatry is the possible antagonism of lysergic acid diethylamide and serotonin. Previously, Gaddum3had shown the effect of such antagonism on smooth muscle. Woolley and Shaw4hypothesized that, if such an antagonism exists, it might be an important factor in schizophrenia. Other drugs of interest behaviorally are mescaline, adrenochrome

Since the introduction of amphotericin B therapy, 60%-80% survival rates have been reported in cryptococcal meningitis, 1-3 a disease which had previously been uniformly fatal. 4 Before the use of this antifungal medication, any therapeutic measure which was credited with producing a remission of a cryptococcal infection with central nervous system involvement was viewed with considerable skepticism. Invariably reference was made to the occasional patient with longterm spontaneous remission. 5 In these cases, however, abnormalities of the spinal fluid persisted even though the patient remained asymptomatic. The present case is unique in that a complete remission of the cryptococcal meningitis, with persistently normal spinal fluid findings for over two years, was accomplished only after amphotericin B was injected directly into the lateral cerebral ventricle. We believe this is the first case to be so treated. The meningitis had failed to respond to the conventional intravenous and intrathecal therapy with this