[Characterization and pharmacological effect on brain damage as a result of cold injury]. / Zur Charakterisierung und pharmakologischen Beeinflussung der durch Kryoläsion ausgelösten Hirnschäden.

Freezing lesion of brain damages the blood-brain-barrier and induces edema. Both injuries are partially separate processes with different progress and diverse response to pharmacological treatment. A very weak lesion fails in to induce edema despite of an enhanced permeation of Evans blue. The injured permeability responds to treatment with dexamethasone or piracetam whereas the edema does not.

[Cholinergic effects of nootropics]. / Zur cholinergen Wirkung von Nootropika.

With respect to the enhancing effect of nootropics on learning and memory, the influence of some of these drugs on the high affinity choline uptake has been investigated. Meclofenoxate competes with choline uptake in vitro because of its similar side chain; other nootropics are without in vitro effects. A single dose of pramiracetam enhances the choline uptake in cortex and hippocampus. Application of meclofenoxate decreases the uptake of choline. Other nootropics lack acute effects. Possible increases of uptake after repeated dosage disappear within 24 h.

[Biochemical characterization and differentiation of dopaminergic supersensitivity in the rat]. / Zur Frage der biochemischen Charakterisierung und Differenzierung der dopaminergen Supersensitivität bei der Ratte.

Parameters of dopamine turnover were measured after developing different forms of behaviour facilitation. The state of denervation supersensitivity is characterized biochemically by diminished dopamine turnover and enhanced receptor sensitivity whereas forms of innervation supersensitivity did not show such alterations.

Changes of dopamine metabolism by hypoxia and effect of nootropic drugs.

An 18 h lasting moderate hypoxia equivalent to 7000 m altitude rises DOPAC level in the caudate nucleus and the mesolimbic area of the rat to about 130%. This elevation is counteracted by a singular high dose of nootropics of the "energy mobilizer" type, but not by vasoactive ones.

[Modification of the recovery of reserpine-induced amine depletion]. / Beeinflussung der Restitution der Reserpin-bedingten Amindepletion.

Recovery of the dopamine storage pool after depletion by reserpine was slightly enhanced by treatment with nandrolone but remained unaffected by nootropic drugs.

[Central depletion of transmitters by reserpine and motor behavior in the rat (author's transl)]. / Zentral Transmitterdepletion durch Reserpin und motorisches Verhalten der Ratte.

Reserpine treatment depletes the catecholamine content in diverse parts of the brain differently. Restoring proceeds slowly with different velocities. Dopaminergic areas tend to a faster repletion than noradrenergic ones. During long-term depletion a recovery of motoric behaviour occurs. This adaptive process is not correlated with the dopamine level in caudate nucleus. The latter depends on the dosage schedule and fails in developing adaptive changes to chronic reserpine administration.

Dopaminergic pathways in the rat central nervous system and rotational behavior.

Unilateral lesion of substantia nigra or ventral tegmental area causes ipsilateral rotational behaviour after receptor stimulation by apomorphine, whereas contralateral rotations were observed after lesion of globus pallidus. The alterations in dopamine and noradrenaline content of relating structures were determined by radiometric microassay. There is no strong correlation between transmitter depletion and motoric asymmetry. The site and extent of lesion seems to be more determinative to motoric disturbances.

Influence of lesion of the median raphe nucleus on motility and dopamine turnover.

Both the spontaneous locomotor activity and the locomotor activity stimulated by apomorphine are enhanced in raphe lesioned animals. The exploratory activity does not show clearcut differences. After unilateral microinjection of dopamine into dopaminergic areas intensity of rotation and dominance of direction are amplified in lesioned animals. Other regions fail to evoke asymmetric or enhanced motoric reactions. The sensitivity of the dopaminergic system of raphe lesioned animals is increased too against unspecific stimulation, but with less strong dominance of direction. The general enhancement of motor activity reflects the inhibitory influence of the serotonergic system. In parallel to the change of behavior we observed a moderate increase of dopamine content connected with an accelerated turnover in lesioned animals.

Pharmacological evidence for dopaminergic pallido-striatal interaction.

In rats the contents in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) of neostriatum (nucleus caudatoputamen, NCP) and paleostriatum (globus pallidus, GP) were measured after transection of the capsula interna (CI) or after injection of 6-hydroxydopamine (6-OHDA; 20 microgram/2 microliter) into the GP of one side. The circling behaviour of the lesioned animals following apomorphine was also studied. 6-OHDA as well as transection decreased the contents in DA and DOPAC in NCP and GP significantly. Following both treatments DA levels in neostriatum were lowest. Nigro-neostriatal pathway lesioned animals (transected or injected with 6-OHDA 16 microgram/2 microliter into substantia nigra, SN) rotated towards the side of lesion after apomorphine (5 mg/kg IP), whereas GP lesioned animals rotated towards the intact side. In animals with both GP and SN lesions at one side turnings of similar intensity towards both sides were seen. In intact rats DA injections (200 microgram/2 microliter) into SN or NCP exhibited contralateral, injections into GP exhibited ipsilateral rotations. The results strengthen the hypothesis on the participation of GP in the regulation of neostriatal content of DA and shows the interaction of the hypothetical dopaminergic pallido-striatal pathway with nigro-neostriatal pathways.

Asymmetric behaviour induced in caudate nucleus lesioned mice: interaction of aminergic and cholinergic agents.

Mice with unilateral caudate lesions exhibit a postural asymmetry or turning towards the lesioned side after application of apomorphine and towards the intact side after oxotremorine injections. The apomorphine effect was counteracted both by oxotremorine and by physostigmine. Both this antagonism and the oxotremorine effect itself were abolished by scopolamine. Adamantine reduced the effectiveness of oxotremorine in inducing asymmetric behaviour. The antagonism of oxotremorine and apomorphine was shifted in parachloramphetamine pretreated mice to an increased apomorphine reaction mode. The significance of lesions became apparent by a 50% decrease of dopamine content in the lesioned side. The 5-hydroxytryptamine content was unchanged. Parachloramphetamine lead to a small alteration of the 5-hydroxytryptamine and 5-hydroxyindolacetic acid content, different in normal and lesioned animals.

Serotonin content in the central nervous system of rats and cholinergic tremor.

Oxotremorine did not alter the level of 5-HT and 5-hydroxyindoleacetic acid in different brain regions. The content of 5-HT in the striatum was diminished by electrolytic lesions of the raphe system, by microinjection of the selective depletor 5,6-dihydroxytryptamine into the raphe system and inhibition of synthesis by pCPA or pCAM. The intensity of oxotremorine-induced tremor was reduced only in some experimental groups without clear-cut correlation to the decreased 5-HT levels. In pCPA-pretreated animals resoring of 5-HT concentration by intrastriatal microinjection of 5-HT and ip administration of 5-HT did not reestablish tremor intensity. There is no evidence that cholinergic tremor is triggered indirectly and depends upon an intact 5-HT system.

Effects of oxotremorine after nigrostriatal lesions in rats.

Bilateral injection of 6-hydroxy-dopamine (6-OH-DA) (8mug/4mul) into the substantia nigra causes a significant decrease of the dopamine content in the nucleus caudatus. The intraventricular application of 6-OH-DA (250 mug/10 mul) induces a considerable decrease of dopamine in the caudate nucleus as well as in the globus pallidus and in the medial septal region. Simultaneous changes in norepinephrine content are less spezific. It has to be assumed that there are dopaminergic nerve endings in the glubus pallidus not originating in the substantia nigra. Only after intraventricular applications of 6-OH-DA s short-term and reversible reduction of oxotremorin-induced tremor has been observed. Lesions of the nigrostriatal pathway cause an impairment of motility, probably elicited by rigidity and akinesia. These symptoms correlate better than the tremor to biochemical changes following nigro-striatal pathway lesions.

[Cholinergic effect on the dopamine turnover in the rat corpus striatum]. / Zur cholinergen Beeinflussung des Dopamin-Umsatzes im Striatum der Ratte

The peripheral administration of oxotremorine caused a significant increase in dihydroxyphenylacetic acid (DOPAC) in the striatum of rats, dopamine (DA) level was unaffected. Injection of oxotremorine into the substantia nigra failed to change the content of dopamine and its acid metabolites homovanillic acid (HVA) and DOPAC in striatum. Injection of oxotremorine or carbachol into the substantia nigra or into the caudate nucleus did not significantly influence the DA-turnover. The partly inconsistent results are discussed in connection with literature data in regard to the existence of excitatory as well as inhibitory cholinergic systems, which are located differently and are involved in the regulation of DA-turnover.