Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats.

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

Effects of L-arginine on penicillin-induced epileptiform activity in rats.

It has been suggested that nitric oxide (NO) is involved in the pathophysiology of epilepsy. Data are, however controversial because it is not clear whether NO has pro- or anticonvulsant effects. The aim of this study was to investigate the effects of NO on penicillin G-induced epileptiform activity. The left cerebral cortex was exposed by craniotomy in urethane-anesthetized Wistar rats. The epileptic activity was produced by intraperitoneal injection of penicillin G (3 million U/kg, i.p.). The ECoG (electrocorticogram) activity was displayed on a four-channel recorder. At 39.7 +/- 5.4 min after penicillin administration, large amplitude sharp waves appeared in the ECoG. Mean spike frequency and mean spike amplitude were calculated as 29.5 +/- 3.2/min and 865 +/- 91 microV, respectively, at the 55th min. 7-Nitroindazole (60 mg/kg, i.p.) injection 30 min before penicillin G administration significantly reduced the latency of epileptiform activity. Intracerebroventricular administration of L-arginine (300 microg/2 microl, i.c.v.) and sodium nitroprusside (100 microg/2 microl, i.c.v.) suppressed epileptiform activity. Saline (2 microl) and D-arginine (300 microg/2 microl, i.c.v.) administration into the cerebral ventricle were completely ineffective on epileptiform activity (P<0.01). These findings suggest that NO may be an endogenous antiepileptic substance.

Do cochlear nuclei contribute to auditory lateralization? A stereological evaluation of neuron numbers.

The aim of this study was to estimate the total number of cells in the subdivisions of the cochlear nucleus (CN) of the rat with unbiased stereological methods. The total number of neurons was determined in both the ventral cochlear nucleus (VCN) and the dorsal cochlear nucleus (DCN) to compare the right and left sides. The total cell numbers were 15,280 in the left VCN, 15,400 in the right VCN, 10,260 in the left DCN, and 10,860 in the right DCN. Comparison of the right and left major subdivisions of the CN of the rat showed that there was no significant difference between the right and left sides of the rat CN. This result indicates that the CNs do not contribute to auditory lateralization in the rat in regard to cell numbers.

The effects of calcium channel blocker, flunarizine on spinal reflexes in the cats.

Effects of calcium channel blocker flunarizine on spinal monosynaptic reflexes were investigated in spinal cats. Flunarizine was administered locally into the spinal cord (10, 50, 100 microM) and intraperitoneally (5, 10, 20 mg/kg). Adult cats (n = 10), weighing 1.5-3 kg were anesthetized with ketamine (50 mg/kg, i.m.) and artificially ventilated. Animals were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. The ventral and dorsal roots of segment L5 were isolated and a pouch of skin was formed at the site of the dissection to allow the exposed tissues to be covered with liquid paraffin. The temperature was kept at 38.5 degrees C with a heating pad. A polyethylene cannula was introduced into the left carotid artery to monitor blood pressure, which was kept above 100 mmHg. The dorsal root of segment L5 was placed on a silver-silver chloride wire electrode for stimulation through an isolation unit. The reflex potentials were recorded from the ipsilateral L5 ventral root, mounted on a silver-silver chloride wire electrode. The systemic (5, 10, 20 mg/kg) and local (50 and 100 microM) dosages of cinnarizin derivative flunarizine significantly decreased the amplitude of reflex response (p < 0.05). Moreover, the latency of the monosynaptic reflexes was increased after administration of the drug (p < 0.05). Voltage-dependent calcium channels in the spinal cord may play an important role to regulate reflex respond.

The effects of calcium channel blocker, flunarizine on spinal reflexes in the cats

Effects of calcium channel blocker flunarizine on spinal monosynaptic reflexes were investigated in spinal cats. Flunarizine was administered locally into the spinal cord (10, 50, 100 microM) and intraperitoneally (5, 10, 20 mg/kg). Adult cats (n = 10), weighing 1.5-3 kg were anesthetized with ketamine (50 mg/kg, i.m.) and artificially ventilated. Animals were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. The ventral and dorsal roots of segment L5 were isolated and a pouch of skin was formed at the site of the dissection to allow the exposed tissues to be covered with liquid paraffin. The temperature was kept at 38.5 degrees C with a heating pad. A polyethylene cannula was introduced into the left carotid artery to monitor blood pressure, which was kept above 100 mmHg. The dorsal root of segment L5 was placed on a silver-silver chloride wire electrode for stimulation through an isolation unit. The reflex potentials were recorded from the ipsilateral L5 ventral root, mounted on a silver-silver chloride wire electrode. The systemic (5, 10, 20 mg/kg) and local (50 and 100 microM) dosages of cinnarizin derivative flunarizine significantly decreased the amplitude of reflex response (p < 0.05). Moreover, the latency of the monosynaptic reflexes was increased after administration of the drug (p < 0.05). Voltage-dependent calcium channels in the spinal cord may play an important role to regulate reflex respond.

The effects of calcium channel blocker, flunarizine on spinal reflexes in the cats.

Effects of calcium channel blocker flunarizine on spinal monosynaptic reflexes were investigated in spinal cats. Flunarizine was administered locally into the spinal cord (10, 50, 100 microM) and intraperitoneally (5, 10, 20 mg/kg). Adult cats (n = 10), weighing 1.5-3 kg were anesthetized with ketamine (50 mg/kg, i.m.) and artificially ventilated. Animals were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. The ventral and dorsal roots of segment L5 were isolated and a pouch of skin was formed at the site of the dissection to allow the exposed tissues to be covered with liquid paraffin. The temperature was kept at 38.5 degrees C with a heating pad. A polyethylene cannula was introduced into the left carotid artery to monitor blood pressure, which was kept above 100 mmHg. The dorsal root of segment L5 was placed on a silver-silver chloride wire electrode for stimulation through an isolation unit. The reflex potentials were recorded from the ipsilateral L5 ventral root, mounted on a silver-silver chloride wire electrode. The systemic (5, 10, 20 mg/kg) and local (50 and 100 microM) dosages of cinnarizin derivative flunarizine significantly decreased the amplitude of reflex response (p < 0.05). Moreover, the latency of the monosynaptic reflexes was increased after administration of the drug (p < 0.05). Voltage-dependent calcium channels in the spinal cord may play an important role to regulate reflex respond.

Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide.

The effect of sodium nitroprusside (SNP) on epileptiform activity elicited by administration of penicillin (500 units) into the somatomotor cortex was studied in anaesthetized rats. No epileptiform activity was observed after intracortical microinjection of SNP (5 and 20 nM). Microinjection of penicillin into the somatomotor cortex induced epileptiform activity in electrocorticograms (ECoG). Epileptiform discharges elicited by penicillin were significantly decreased by SNP. The effect of SNP appeared within 1 min of application and lasted for 2-5 min. The inhibitory effect of SNP on epileptiform activity could be prevented by pretreatment with methylene blue (20 nM), a soluble guanylate cyclase inhibitor. Prior injection of haemoglobin (5 microliter), a nitric oxide (NO) scavenger, prevented the anticonvulsant effect of SNP. These results suggest that NO may be an endogenous anticonvulsant substance.

The effects of the purinergic system on digitalis-induced epileptiform activity.

It has been suggested that endogenous chemical substances, such as adenosine, released during a seizure attack, may act as anticonvulsants in vivo. We have investigated electrophysiologically the effects of purinoceptor agonists and antagonists on the epileptiform activity induced by intracortical digitalis in anesthetized rats. Intracortical injections of 1, 2, or 4 micrograms digitalis (desacetyl lanatocid C) caused an epileptiform electrocorticogram (ECoG). The application of adenosine (25 or 100 microM) or adenosine triphosphate (ATP) (3 mM) after desacetyl lanatocid C blocked the epileptiform activity. beta, gamma-Methylene ATP (0.1-0.8 mM), a stable analog of ATP, produced inhibition and then death. The epileptogenic effect of desacetyl lanatocid C was enhanced by theophylline (1 mM); however, suramin (1 mM) changed the pattern of epilepsy. These results indicate that the purinergic system may be involved in the mechanism of action of digitalis glycosides.

Microstimulation of the supplementary motor area (SMA) in the awake monkey.

The supplementary motor area of three Macaca fascicularis was mapped using intracortical microstimulation (ICMS). Both forelimb and hindlimb movements were evoked using currents of 30 microA or less. However, thresholds for evoking movements were higher than those in the primary motor cortex. Proximal motor effects predominated, but distal joint movements were also elicited. Forelimb points were clustered in mesial cortex of area 6, anterior to the precentral hindlimb and tail region. Distal joint effects were located deep in the cortex, intermingled with proximal effects. Hindlimb response which were less spatially localized, were found both ventral to the forelimb area, in the dorsal bank of the cingulate sulcus, and in mesial cortex, well anterior to area 4. No movements of facial muscles were elicited. Injections of HRP were made into the spinal cord at the cervical level in two animals and the lumbar level in the third one. An area of labelled cells was seen in mesial area 6 which corresponded closely to the region from which ICMS effects were elicited. No movements were evoked from the anterior portions of the fundal region of the cingulate sulcus which were also labelled.

Corticospinal neurones of the supplementary motor area of monkeys. A single unit study.

The direct projection from the supplementary motor area (SMA) to the spinal cord was investigated in six monkeys by means of antidromic identification of single SMA neurones. The exploration concentrated on that portion of medial area 6 from which movements were found to be elicited by stimulation at intensities of less than 30 microA in an earlier study, but also included some of medial area 4. Of 315 identified corticofugal projection neurones, 234 were found to be localized within medial area 6; of these only one third (76 cells) were corticospinal cells and the remaining two thirds were neurones which projected to the brainstem. The conduction velocities of the descending projection neurones of the SMA were slow (modal value: 10 m/s). Corticospinal cells of the SMA were found up to 6 mm rostral to the boundary between areas 4 and 6. Corticospinal neurones activated antidromically from the cervical but not from the lumbar cord ('cervico-thoracic' neurones) were concentrated in the mesial cortex; 'lumbo-sacral' neurones were found both in the dorsal cortex and the dorsal bank of the cingulate sulcus. However, there was considerable intermingling between the two types of projection neurones and there was no separation in the rostro-caudal direction. Similarly, projection neurones receiving orthodromic inputs from the somatotopical subdivisions of the precentral cortex were not segregated, but were intermingled in the entire rostro-caudal extent of the SMA. It is concluded that there is a clustering of corticospinal neurones in the SMA according to their most caudal segmental projection. However, no rostro-caudal differentiation into face, arm and leg areas was established. This observation is consistent with the results of a previous study in which corticospinal neurones in the SMA were labelled with anatomical tracers and efferent zones were investigated with intra-cortical microstimulation (Macpherson et al. 1982).

Electrocorticographic effects of topically applied scopolamine.

The electrocorticographic effects of topically applied scopolamine were investigated in unanesthetized cats with high cervical transection. After subpial injection of 30 cumu scopolamine in concentrations of 10 to 20%, large amplitude intermittent sharp waves appeared in the electrocorticogram, which developed into long-lasting paroxysmal activity. This effect was antagonized by intravenous eserine, 0.1 mg/kg, when it was produced by topical scopolamine in low dosage. The acoustically evoked cortical response and the generalized epileptiform activity produced by topical succinylcholine disappeared after topical scopolamine in low dosage. It is suggested that the seizure-suppressing effect of scopolamine may be due to its cholinolytic action. The convulsive activity of topical scopolamine in high concentrations may be accounted for by its depolarizing, synchronizing, disinhibiting, and acetylcholine-releasing effects.

Electrocorticographic effects of topically applied ouabain, epinephrine and bicuculline.

The effects of topically applied ouabain, epinephrine and bicuculline on the electrocorticographic activity were studied in unanesthetized cats with high cervical transection. Ouabain in a concentration of 25 X 10(-6) induced single intermittent spikes or paroxysms lasting for about 4-10 min. A 5% solution of bicuculline also induced paroxyms which lasted for many hours and were suppressed by topical epinephrine. Ouabain paroxysms became more vigorous when applied after epinephrine and bicuculline. Topical epinephrine dimished the ouabain discharges and the click evoked cortical responses. It is suggested that the epileptogenic activity of ouabain and bicuculline and its antagonization by epinephrine can be accounted for by the antagonistic effects of these agents on the electrogenic ion pumps such as inhibition and stimulation of the (Na + K) ATPase activity, respectively.