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For the evaluation of the prognosis of the melanoma malignum (MM) several markers have been used before but none of them was powerful enough therefore a search for new markers is justified. The authors have studied the expression of three metastasis associated proteins, nm23, CD44v3 and MMP2 collagenase using immunohistochemistry on the paraffin embedded tissue samples of 22 primary skin melanomas. The expression of these markers was independent from the thickness of the tumor or the clinical stage of the disease. Due to the frequent discrepancy between the thickness of the tumor and the actual outcome of the disease, they regrouped the cases according to the biological behaviour of the tumor into non-metastatic, lymph node-metastatic and organ metastatic forms. Based on the MMP2 expression +/- tumors can be found but the expression does not correspond to the biological behaviour of MM while decreased nm23 expression characterized the lymph node metastatic tumors. CD44v3 expression was rare in MM and occurred at low level, however, when expressed it showed significant correlation to the organ metastatic phenotype. The authors concluded that the classic invasion markers in case of MM have a limited potential in the characterisation of the invasive phenotype, therefore more sensitive markers are necessary.

The development of the wakefulness-sleep cycle and neuronal responsiveness was studied on freely moving 1-, 3-, 5- and 7-day-old rats. Semimicroelectrodes were implanted under ether anaesthesia for multiunit activity (MUA) recording from the mesencephalic reticular formation (MRF) and basal forebrain area (FB). Following recovery from surgery and between the recording sessions pups were put back to the nest to be fed by their mothers. In a temperature-controlled environment continuous MUA records were made between 16:00–18:00 and 19:00–21:00 h. In the MRF and FB the MUA was high during wakefulness, it decreased to a stable low level in quiet sleep and appeared to reach the highest values in paradoxical sleep. Neurone populations in the MRF and FB responded to somatosensory (air puffs), visual (flicker) and acoustic (1100 Hz) stimulation by a significant increase of MUA from the first day of life. In the MRF the rate of responsiveness increased during the first postnatal week; however, MUA responses to different stimuli exhibited different developmental time-courses. A high rate of responsiveness to each stimulus was characteristic of FB units. This neonatal ‘supersensitivity’ tended to decrease with age and the time-course of developmental changes proved to be modality-dependent.

Multiple unit activity was recorded in newborn, 5-day old and adult unanesthetized and succinylcholine-immobilized rats. The development of neuronal responsiveness of mesencephalic reticular formation and basal fore-brain area was studied to various sensory modalities. It was found that both neuronal populations responded to acoustic and visual stimulation by a significant increase in the frequency of amplitude discriminated discharges as early as the first week of life. Somatosensory stimulation elicited a strong activation of both brain regions in new born rats, and this type of responsiveness decreased during development. It was proposed that the neonatal CNS is capable of processing sensory information. The high level of somatosensory responsiveness is of great importance in the survival of the newborn animal, possibly because this is the neuronal mechanism underlying elementary learning processes and memory formation.

SUMMARY Cortical e.e.g. and multiple unit activity (m.u.a.) of the mesencephalic reticular formation, the anterior hypothalamic area, the basal nuclear group of the amygdala and the dorsal hippocampus were studied before and following i.p. injection of different doses of ketamine hydrochloride and a barbiturate in cats with chronically implanted electrodes. Barbiturate administration resulted in a rapid decrease in m.u.a. in the mesencephalic reticular formation which was accompanied by a significant decrease of activity in the limbic structures. No m.u.a. response was observed to visual, acoustic or somato-sensory stimulation or to pain. The m.u.a. of the mesencephalic reticular formation and limbic structures increased gradually following ketamine injection. Intermittent or continuous hypersynchronous activity was characteristic in the cortical e.e.g. During the hypersynchronous activity the responsiveness of m.u.a. in the mesencephalic reticular formation, to visual and acoustic stimuli, was blocked. Somatosensory and painful stimulation, however, resulted in a significant increase in the activity both of the mesencephalic reticular formation and of the limbic neuronal pools

Exploratory behavior (GMA) and habituation rate (IH) were studied in an open-field situation in normal and adrenalectomized rats. Following this procedure the rats were subjected to passive avoidance learning (PA). Wide-spreading individual differences were observed in the exploratory behavior and the tendency of habituation of normal rats. As compared to the normal values, either the adrenalectomy which was performed 24 hr, 7 days and 28 days prior to the experiments or the ACTH and hydrocortisone treatment failed to modify the GMA and the IH significantly. An improvement of PA was found in the normal rats following ACTH and hydrocortisone treatment. In the adrenalectomized animals the hydrocortisone proved to be effective, whereas ACTH did not influence PA. No correlation was found between GMA, IH versus PA values and the influence of ACTH and hydrocortisone administration on these parameters. It is concluded that the direction of PA is unpredictable on the basis of the open-field test performed on R-Amsterdam strain of rats, and the effect of ACTH on passive avoidance learning is mediated through the adrenal glands.

Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness.

Cortical EEG and multiunit activity (MUA) of the mesencephalic reticular formation (MRF), area hypothalami anterior (AH) and the nucleus amygdalae basalis (AMY) were studied before and after different doses of alphadione (Althesin) and hexobarbitone (Evipan-Natrium) given to cats with chronically implanted electrodes. Non-anaesthetic doses of alphadione (0.15 ml/kg; 0.3 ml/kg; 0.6 ml/kg and 1.2 ml/kg i.p.) had sedative effects decreasing selectively the MUA in the MRF. In doses of 2.0 ml/kg, 2.4 ml/kg and 3.0 ml/kg i.p., alphadione induced anaesthesia which was associated with a rapid decrease of MUA in the MRF and by a gradual decrease of activity in the AH and AMY. The i.p. dose of 3.0 ml/kg abolished MUA responses of the reticular formation to acoustic, visual and somatic stimulation but failed to block responses to pain. Deep anaesthesia with lasting analgesia could be maintained by i.v. infusion (0.075 ml/kg/min). This procedure blocked the responsiveness to painful stimulation while pharyngeal and laryngeal reflexes were maintained. Hexobarbitone in a dose of 20.0 mg/kg i.p. did not produce anaesthesia in the cat. Administration of 40.0 mg/kg i.p. resulted in a rapid decrease of MUA in the MRF, AH and AMY, MUA responses to each stimulation were abolished and the pharyngeal reflex was blocked.

Neonatal brain (whole brain minus cerebral hemispheres) dopamine (DA) and norepinephrine (NE) concentrations (pg/microgram protein) were studied 30 min after an injection of L-DOPA methyl ester (50 mg/kg); haloperidol (1 mg/kg); D-amphetamine sulfate (0.5 mg/kg); saline only or no treatment. Catecholamines were assayed on the day of birth (postnatal day 1) and postnatal day 7 by high performance liquid chromatography coupled with an electrochemical detector for catecholamines (CA). When L-DOPA was administered there was a selective 7 X (postnatal day 1) or 3 X (day 7) increase in brain DA when compared to saline controls. Haloperidol pretreatment on either day prevented these increases after L-DOPA. These findings constitute biochemical evidence for selective elevation of brain DA during the first postnatal week of life after L-DOPA administration in a dosage that is also capable of enhancing the coordination required for swimming behavior.

The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30–50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.

Multiunit activity (MUA) of the mesencephalic reticular formation (MRF) was recorded on freely moving 1 to 21-days-old young as well as adult rats. Consistent state-dependent changes in the frequency of amplitude discriminated cell discharges were observed in association with wakefulness and sleep cycle from the first day of life, and MRF neuron populations were found to gain adult-like functional characteristics of spontaneous activity by the 9th-11th postnatal day. MRF units were capable of responding to somatosensory, visual and acoustic stimulation by a significant activation from Day 1. As development proceeded, rate of responsiveness appeared to increase, however, MUA responses to different sensory modalities exhibited different developmental time-courses. High rate of responsiveness to somatosensory stimulation was characteristic of the newborn rat. Magnitude of somatosensory responses increased remarkably during the first three postnatal days reaching adult values around this age and only moderate alteration of response patterns could be detected afterwards. The MRF MUA responses to visual and acoustic stimulation increased during the first week of life and, following a striking decline of responsiveness occurring at the time of opening of eyes and external auditory meati (Day 13), visual and acoustic responses gained the adult properties by the 17th-19th postnatal day.

Recording of multiunit activity (MUA) from the mesencephalic reticular formation (MRF) of freely behaving rats, aged between 1 and 120 days, revealed that state dependent changes in cell firing associated with wakefulness and sleep cycle were present from the first day of life. The MRF neuron populations were found to gain the adult-like functional properties by the 9-11th postnatal day. The paradoxical sleep phases attained adult characteristics by day 12-13 and the average duration of slow wave sleep episodes was that of adult rats at the end of the 4th week, the maturation of sleep behavior was completed at the age of day 33-35.