Lateralized asymmetrical state-dependent learning produced by kindled convulsions from the rat hippocampus

The ability of hippocampal kindled convulsions to support state-dependency (or cue-conditioning) was investigated. Wistar rats were implanted unilaterally in the left or right ventral hippocampus and kindled until generalized convulsions developed. The animals were then trained and tested in a one-trial step-through inhibitory avoidance task under either normal or altered-state (10 min after a convulsion) conditions. Four group conditions of training- vs testing-state were employed for each hemisphere: normal-normal (N/N), convulsed-convulsed (C/C), convulsed-normal (C/N), and normal-convulsed (N/C). Results indicated that left- or right-kindled animals trained and tested in the normal state (N/N) retained the task well. For the left-kindled groups, all other conditions demonstrated impaired recall. For the right-kindled groups, the C/C group showed recall comparable to the N/N group, while C/N animals indicated only slightly impaired recall; only the N/C group was markedly impaired. It seems the right hippocampus tends to give asymmetrical state-dependency after a convulsion, while results for the left hippocampus are less clear. Possible underlying mechanisms are discussed.     

Substance P-induced tachycardia in the anaesthetized rat

In pentobarbital-chloralose-anaesthetized rats, pretreated with hexamethonium and atropine the mechanism by which substance P (SP) causes tachycardia was analysed. Substance P, when infused i.v. at doses between 0.49 nmol and 1.52 nmol elicited a marked, dose-dependent tachycardia, which was reduced to less than half by propranolol, 0.1 mg kg-1. Furthermore, the SP-induced tachycardia was reduced to about 1/10 of control by guanethidine. Further, the tachycardia, which could also be elicited in pithed rats, was antagonized by the SP-receptor blocker Spantide, but these results must be taken with care since Spantide itself caused a pronounced and long-lasting depressor response. It is hypothesized that SP causes tachycardia by exciting specific receptors on the stellate ganglia, which leads to an activation of adrenergic fibres to the sinus node.     

Inhibition of sound-induced convulsions by metoprine in the audiogenic seizure susceptible rat

Metoprine which increases brain histamine by blocking its methylation, was recently demonstrated to inhibit electrically induced tonic convulsions in rats. Its effect was now tested on audiogenic convulsions in genetically audiogenic seizure sensitive rats. Metoprine (20 mg/kg, i.p.) reduced the severity of seizures significantly 4 and 28 h after drug administration. Also the duration of convulsions was significantly decreased. These results agree with an involvement of histaminergic neurons in convulsive phenomena perhaps as a part of an anticonvulsive inhibitory transmitter system.     

Dose-dependent effects of taurine on convulsions induced by hypoxia in the rat

Taurine and phenobarbitone had protective effects in hypoxia-induced convulsions in rats. The dose of taurine was found to be a critical factor. Thus, while 50 mg/kg of taurine was most effective in suppressing onset of convulsions, 100 mg/kg adversely affected its anticonvulsant action.     

Lateralized state-dependent learning produced by hippocampal kindled convulsions: effect of split-brain

In previous experiments, it was demonstrated that convulsions kindled from a ventral hippocampal focus in rats supported state-dependent learning which tended to lateralized to, and asymmetrical in, the right hemisphere. The question of the differential contribution of the left and right hippocampus to the production of state-dependency can best be addressed through confining the seizure to one or the other hemisphere via commissurotomy. In the present investigation, then, commissurally-intact and split-brain rats were implanted with bilateral hippocampal electrodes, then a left or a right focus was kindled. Later behavioral testing in an aversive inhibitory avoidance (IA) paradigm, revealed that intact animals, both left and right kindled groups, displayed good state-dependency. Split-brain animals, however, exhibited differential state-dependent responses to convulsive stimulation. Those kindled in the left hippocampus showed good retention when the conditions of seizure during training and testing were the same (same-state conditions), while showing deficient recall in changed-state conditions (a good state-dependent profile). On the other hand, those kindled in the right hippocampus displayed good retention of the IA experience in both same- and changed-state conditions. Differential recall after a left versus a right hippocampal convulsion in split-brain animals could not be accounted for in terms of differential seizure parameters, laterality of afterdischarge, extent of extracommissural damage or the extent of the actual transection. Possible mechanisms underlying this effect were discussed.     

Long-lasting potentiation produced by a phorbol ester in the hippocampus of the anaesthetized rat is not associated with a persistent enhanced release of excitatory amino acids

The relationship between the long-lasting enhancement of synaptic transmission produced by a phorbol ester and the release of endogenous excitatory amino acids has been investigated in the CA1 hippocampal region of the anaesthetized rat. Using the push-pull technique, the concentration of glutamate and aspartate was assayed in the perfusate by high-pressure liquid chromatography. Application of phorbol 12-13 diacetate produced a long lasting enhancement of the field excitatory postsynaptic potential (EPSP) (over 2 h). This was associated with a brief (10 min) significant increase in the release of glutamate and aspartate. However, subsequently the levels of the amino acids in the perfusate were not different from the pre-drug (control) levels although the field EPSP was still enhanced. It is concluded that the long-lasting enhancement produced by phorbol ester is not due to a persistent increase in the release of excitatory amino acids.     

Acidaemia produced by spinal stimulation in the pithed rat

1. Electrical stimulation of the thoraco-lumbar spinal nervous outflow in the pithed rat preparation produces a fall in arterial blood pH.2. A component of the acidaemic response results from stimulation of skeletal muscle, since the acidaemic response is reduced when contractions of muscle are blocked with gallamine.3. The residual acidaemic response in gallamine-treated rats is reduced by adrenalectomy, suggesting that catecholamines liberated from the adrenal medulla may mediate part of the effect.4. Guanethidine reduces the acidaemic response remaining in adrenalectomized, gallamine-treated rats, suggesting that the effect of noradrenaline released from sympathetic nerve endings contributes to the fall in pH.5. Neither phenoxybenzamine nor propanolol alone significantly reduces the acidaemic response in gallamine-treated rats, but a combination of the two antagonists almost abolishes the effect. Hence the acidaemia is mediated through effects of catecholamines on both alpha- and beta-adreno-receptors.6. Since acidaemia affects responses to sympathetic nerve stimulation and sympathomimetic amines, the significance of these observations is discussed with reference to the use of the pithed rat preparation for assessment of drugs affecting adrenergic mechanisms.     

Motor responses elicited by local electrical stimulation of the distal colon in the anaesthetized rat

A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro-effector systems. The adrenergic neuron-blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation ('off' or 'rebound' contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as 'rebound' contractions which were preceded by a relaxation. Such TTX-resistant responses may be myogenic, but a neurogenic origin cannot be excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine- and TTX-resistant motor responses.     

Enhanced intestinal motility influences absorption in anaesthetized rat

The subject of this investigation was to study influence of the intestinal motility on absorption of 3‐o‐methyl‐D ‐glucose (3‐OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin^® and Rapinovet^®. A segment of duodenum, approximately 10 cm, was perfused single‐pass with saline containing unlabelled and radioactive 3‐OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet^®, which showed a ‘burst‐type’ pattern resembling migrating motor complex (MMC). Absorption of 3‐OMG in rats with MMC‐like motility appears to be lower than in rats with fed‐like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r ²=0.75) between intestinal activity (fed) and absorption of 3‐OMG, but not with absorption of mannitol. The carrier‐mediated absorption of 3‐OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.     

Fever produced in the rat by intracerebralE. coli endotoxin

Summary E. coli endotoxin introduced into the brain ventricles or into various brain areas raises the body temperature of conscious rats. Endotoxin-sensitive sites were found within the anterior hypothalamus and the lower brainstem. The increase in temperature (T) after microinjection of endotoxin into the anterior hypothalamic nucleus was dose-dependent. Endotoxin injected into the ventricles produced monophasic hyperthermia, but microinjections into the anterior hypothalamus produced monophasic or biphasic types of hyperthermia. The second and third microinjections of endotoxin into the anterior hypothalamic nucleus subsequently caused higher responses in T, but not in the rate of temperature change. The effects of the fourth and further microinjections were the same as those of the third, and no tolerance developed for 24 days. The observations of behaviour, vegetative reactions, skin temperature, and carbon dioxide production indicated that the rise in the rat body temperature induced by endotoxin represents fever and that the heat is gained, at an ambient temperature of 22°C, mainly through skin vessel vasoconstriction. Aspirin abolished and reversed fever induced by endotoxin, while hydrocortisone was without effect.     

Sensory interactive zones in the rat cerebral cortex

The acoustic, somatosensory and visual areas of the rat cerebral cortex were mapped in view of overlapping regions, giving polysensory evoked responses. In case of each pair of modalities overlapping areas were found between the cortical representations. The evoked potentials of two different modalities show occlusive and facilitatory interactions in these overlapping areas. In the "core" region of these areas, points with especially high values of occlusion are concentrated while at the periphery weak occlusion or even facilitation is characteristic. It is supposed that the polysensory areas interposed between primary sensory fields represent not only areas with mixed responsiveness but also stage for real physiological interactions between different sensory systems.