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E Laschka

Publications and source records attributed to E Laschka.

9 recordsLinked to original sources
PubMed1978

Site of naloxone-precipitated opiate withdrawal dissociates from that at which apomorphine reinitiates this phenomenon.

The site of action of naloxone to induce jumping in morphine tolerant/dependent rats appears to be dissociated from structures where apomorphine initiates its action to reinduce jumping in previously withdrawn animals. These findings suggest that dopaminergic pathways do not directly affect the neuronal circuit involved in withdrawal jumping behavior, but instead exert a facilitatory influence on neurons that become supersensitive during the state of withdrawal. Thus, an increased response to apomorphine during naloxone-precipitated opiate withdrawal does not necessarily imply a specific supersensitivity of the dopaminergic system.

Animals↗
PubMed1977

Sites of action of morphine involved in the development of physical dependence in rats. III. Autoradiographic studies.

Morphine withdrawal was precipitated by injection of 3H-naloxone into restricted parts of the ventricular system of rats made tolerant to and dependent on morphine by repeated pellet implantation. The spread of the drug was evaluated by autoradiography and compared with the withdrawal signs precipitated in the same experiment. When the antagonist could spread into the tissue surrounding the 4th ventricle and the caudal parts of the aqueduct (penetration depth about 1.5 mm), a strong withdrawal syndrome was displayed. In contrast, only weak or no withdrawal signs were observed when the spread of naloxone was restricted to the surroundings of the lateral ventricles, the 3rd ventricle, and the rostromedial parts of the aqueduct. The same was true when the spread of the antagonist was limited to the ventral surface of the brain stem. It is concluded that structures located in the anterior part of the fossa Rhomboidea, and possibly also in the caudal part of the periaqueductal grey matter, are sites for the development of physical dependence on morphine giving rise to the withdrawal signs studied in these experiments.

Animals↗
PubMed1976

Sites of action of morphine involved in the development of physical dependence in rats. I. Comparison of precipitated morphine withdrawal after intraperitoneal and intraventricular injection of morphine antagonists.

In rats made dependent on morphine by implantation of morphine pellets, withdrawal, as precipitated by intraventricular injection of morphine antagonists, was compared to withdrawal as precipitated by systemic antagonist application. The results, most clearly those obtained with a hydrophilic compound, diallyl-nor-morphinium-bromide, point to periventricularly located sites of action for the release of most withdrawal signs by antagonists. Jumping, reaching only low levels after i.ventr. injection of levallorphan and nalorphine, was very pronounced when the benzomorphane derivative SH 254, was used. In the case of writhing and diarrhea, the situation is more complicated. Possibly, central as well as peripheral mechanisms are involved in the expression of these signs.

Animals↗
PubMed1976

Sites of action of morphine involved in the development of physical dependence in rats. II. Morphine withdrawal precipitated by application of morphine antagonists into restricted parts of the ventricular system and by microinjection into various brain areas.

Morphine withdrawal was precipitated by injection of various morphine antagonists into restricted parts of the ventricular system or by microinjection of levallorphan into specific brain areas of rats made dependent on morphine by repeated pellet implantation. When the antagonists could spread only within the lateral ventricles and the 3rd ventricle, a weak withdrawal syndrome was induced; by antagonist administration into the restricted 4th ventricle, however, strong withdrawal signs like jumping were elicited even at small dosages. In microinjection experiments, structures in the midbrain and the lower brain stem proved to be the most sensitive to antagonist action. Although microinjections into thalamic nuclei also had some effect, it could not be excluded that the effects were due to uncontrolled spreading of the drug. This became especially clear from experiments with tritium-labeled levallorphan. It is concluded that brain structures located in the anterior parts of the floor of the 4th ventricle and/or caudal parts of the periaqueductal gray matter are important sites of action for the development of physical dependence on morphine.

Animals↗
PubMed1976

Activity of the nigro-striatal dopaminergic system during precipitated morphine withdrawal investigated in rats with acute unilateral inactivation of the striatum.

The activity of the striatal dopamine system during precipitated morphine withdrawl was studied in rats using a model in which the striatum was unilaterally inactivated by the local injection of KCl. In naive rats dopamine agonists administered just prior to KCL induced ipsilateral turning or circling, while dopamine antagonists in the same situation caused contralateral turning. Withdrawal precipitated by morphine antagonists in rats made dependent by repeated implantation of morphine pellets induced contralateral circling during unilateral inactivation of the striatum. This contralateral circling was only slightly enhanced by haloperidol, but strongly enhanced by a low dosage of apomorphine as well as by some weak dopamine agonists such as CB 154 or By 101. However, high doses of apomorphine completely reversed the withdrawal-induced contralateral circling into ipsilateral circling. Other dopamine agonists, such as d-amphetamine, L-Dopa and piribedil, did not abolish the withdrawal-induced contralateral circling, however, they caused the appearance of an additional ipsilateral circling. Other types of drugs which are known to intensify withdrawal-induced jumping (desipramine, atropine, caffeine) enhanced contralateral circling. There are also other parallels jumping and contralateral circling induced by withdrawal. The direction of naloxone-induced asymmetric behaviour during acute unilateral inactivation of the striatum suggests that striatal dopaminergic activity is reduced during precipitated withdrawal; the other results reported point to the possiblity that extrastriatal dopaminergic mechanisms or different dopamine receptor types within the striatum are involved.

Animals↗
PubMed1976

The role of dopamine in withdrawal jumping in morphine dependent rats.

The role of dopamine (DA) in precipitated withdrawal jumping was studied in morphine dependent rats. Pretreatment with various dopaminergic agonists induced a dose-dependent increase in naloxone induced jumping. Pimocide totally blocked the facilitatory effect of piribedil while naloxone induced jumping was not dose-dependently decreased. Biochemical measurements revealed that during precipitated withdrawal the level of DA was elevated and the accumulation of 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) after probenecid as well as the level of 3-methoxytyramine in the striatum was reduced. Unilateral inactivation of the caudate by local injection of KCl induced contralateral circling during withdrawal. Additional systemic haloperidol pretreatment did not change the direction of circling while additional apomorphine pretreatment changed the direction to ipsilateral and increased the circling rate highly. These latter as well as the biochemical findings strongly suggest an inhibition of striatal DA-mechanisms during withdrawal. The apparent contradiction of these findings to the above finding showing a facilitatroy role of DA-agonists on jumping is discussed.

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