Peter Lomax

The Gerbil as a Model for the Study of the Epilepsies.: Seizure Patterns and Ontogenesis*

A new strain of selectively bred seizure‐sensitive Mongolian gerbils is described. These WJL/UC gerbils exhibit stereotyped seizures in response to increased stimulus input that can be rated on a seven‐point scale of severity. Integrated motor activity during seizures and latency and duration of seizures are related to severity. Susceptibility to seizures starts at 9 weeks and reaches 97% at 6 months. The severity increases from a mean of 1.2 at 2 months to 4.1 at 6 months of age. Death in seizure is rare. These attributes make the WJL/UC seizure‐sensitive Mongolian gerbil suitable for testing as an animal model valid for study of the epilepsies.

Morphine hyperthermia in the rat: An action of the central thermostats

The mechanism underlying the hyperthermic response to low doses of morphine has been investigated in rats. Doses of morphine sulfate less than 10 mg/kg i.p. caused a rise in body temperature accompanied by vasoconstriction of the cutaneous blood vessels of the tail. This hyperthermia, unlike the hypothermia following higher doses of morphine was not blocked by naloxone nor did tolerance develop to the response. Injections directly into the hypothalamus suggested that, as with the fall in temperature after high doses of morphine, the hyperthermic effect is also due to an action on the preoptic/anterior hypothalamic thermoregulatory centers. Experiments measuring thermoregulatory behavior showed that rats delayed escaping from a heat load after low doses of morphine even though their core temperature was rising. These results suggest that low doses of morphine raise the set point of the central thermostats in rats resulting in a hyperthermia mediated, at least in part, by decreased cutaneous heat loss.

Postmenopausal hot flushes: A disorder of thermoregulation

The changes in cutaneous and body temperature and cutaneous conductance during hot flushes in eight postmenopausal women were studied. The vasomotor changes occurred approx. 45 sec after the patients experienced the initial subjective symptoms of the attacks. The rise in skin conductance appeared to be a more reliable index of the flushing episode than did the change in skin temperature. On the basis of the changes recorded it is suggested that the hot flush syndrome may represent a specific thermoregulatory disorder rather than being due to a non-specific central autonomic discharge. The episodes may be triggered by a neuroendocrine imbalance following the disruption of ovarian function and fall in estrogen production. In assessing the frequency and severity of hot flushes, and the effects of treatment, objective measurements of skin and core temperature and skin conductance should replace subjective criteria.

Hypothermia following systematic and intracerebral injection of oxotremorine in the rat

Abstract Intravenous administration of oxotremorine leads to marked hypothermia in the rat. The fall in core temperature can be reproduced by microinjection of oxotremorine into the preoptic/anterior hypothalamic nuclei. The hypothermie response to intracerebral oxo-tremorine is blocked by prior intraperitoneal administration of atropine or trihexyphenidyl. Injection of carbachol into the anterior hypothalamus led to a fall in temperature of the same order as that produced by oxotremorine. It is concluded that the hypothermie action of oxotremorine is due to a direct effect on the thermoregulatory centers. These results also suggest that the effect of oxotremorine on body temperature is due to a muscarinic action of the drug.

Drugs and body temperature.

Publisher Summary The mechanisms involved in the regulation of internal body temperature continue to receive the attention of many investigators. The effects of drugs on thermoregulation have been extensively studied and attempts have been made to determine the sites and mechanisms of drug action in the light of this newer knowledge. Any system of the complexity of that concerned in temperature regulation would be expected to be particularly susceptible to disturbance by the action of drugs. Owing to the well-regulated negative feed-back control of the system, however, any impairment tends to be compensated for, so that, in most cases, deviations from the set point are small in magnitude. Also, there are several instances where the action of the drug on peripheral structures involved in temperature regulation is opposite in effect to that exerted on the central thermoceptive structures. Such factors often render it difficult to determine the precise mechanisms by which a drug-induced change in core temperature is brought about. In this chapter, attention is directed mainly to agents for which there is evidence indicating a direct action on the thermoregulatory centers in the central nervous system.

Cholinergic and adrenergic interactions in the thermoregulatory centers of the rat

Summary Systemic administration of pilocarpine causes a fall in body temperature in the rat. This effect can be reproduced by direct injection of the drug into the rostral hypothalamic thermoregulatory centers. The fall in temperature following systemic administration of pilocarpine can be attenuated or blocked by prior injection of norepinephrine into the rostral hypothalamus. Injection of α-blocking agents into the thermoregulatory centers, immediately preceding injection of norepinephrine at the same site, prevents the inhibitory effect of norepinephrine on the hypothermic response to systemic pilocarpine. It appears that temperature regulation involves a cholinergic link in the rostral hypothalamus. Catecholamines may also play a role in the control of body temperature by changing the degree of polarization of these cholinergic neurons and thus adjusting the sensitivity of the thermoregulatory centers. Such an adjustment of the membrane potentials by endogenous catecholamines could be a factor in the physiological regulation of the set point of the central thermostat.

Sites and mechanisms of action of histamine in the central thermoregulatory pathways of the rat

Abstract Behavioural thermoregulation studies, in which rats were exposed to a heat lamp, indicated that the fall in temperature induced by systemic injection of histidine is due to activation of efferent heat loss pathways. This response was blocked by injection of the H 2 -receptor antagonist, burimamide into the third ventricle. The hypothermia following intraventricular injection of histamine appears to be due to a lowering of the set point of the rostral hypothalamic thermostat. Pyrilamine, an H 1 -receptor antagonist, prevented this effect of histamine.

Ethanol-Induced Hypothermia in the Rat

Ethanol (0.5-3.2g x kg-1 i.p.) caused a dose-dependent fall in body temperature in rats. A dose of 1.5g x kg-1 i.p. led to a fall of 1.6 +/- 0.20 degrees C over 60 min at an environmental temperature of 18 +/- 1 degrees C. There was no evidence of acute tolerance when the hypothermic response was elicited by the same dose of ethanol (0.7--20.0g x kg-1 i.p.) 24 h later; indeed the second response was consistently, although not significantly, greater than the first. Behavioral thermoregulatory studies indicated that the fall in temperature after ethanol is due, at least in part, to a downward setting in the thermoregulatory set point. These results suggest that the rat may be a suitable animal model for a study of accidental hypothermia following ethanol ingestion and exposure to low environmental temperatures.

Postmenopausal hot flushes and their management.

Hot flushes are frequently incapacitating to the patient and the severe vasomotor disturbances may seriously impair normal daily life. This review attempts to provide an understanding of the pathophysiology of the hot flush as a basis for rationale therapy for each individual patient. The physiological mechanisms controlling body temperature are discussed briefly, and the changes in the system which precipitate the menopausal hot flush are detailed. The neuroendocrine events leading to the onset of the flushing syndrome are then considered. Finally, the therapeutic strategies which may be used in the management of the affected patient are discussed.

Hippocampal Neuron Density and Seizures in the Mongolian Gerbil

Summary: Mongolian gerbils of the seizure‐sensitive strain exhibit epileptic seizures in relation to changes in the environment, a characteristic which has been increased to about 100% by inbreeding. The seizures vary from animal to animal but are rather stable in the individual animal, which makes it possible to study the neuron densities in the hippocampus of the gerbil in relation to seizure type and seizure intensity. Five groups of gerbils with seizures ranging from minor movements and motor arrest to intense generalized convulsions were investigated with a quantitative method including cell counting by light microscope and estimation of possible brain shrinkage, as well as determination of nucleoli and nuclei diameters. The cell densities were determined in different areas of the pyramidal cells of the hippocampus (H‐fields). The study discloses a reduction of cell densities in fields H2 and H3 in relation to intense generalized convulsions. It is suggested that the reduction in cell density in field H2 is a result of seizure activity, whereas the field H3 cell loss can be the result of both the hypoxia and the seizure activity.