Biomedical subjects
Publications and source records attributed to K Andreas.
The development of ethanol preference behaviour in rats is connected with a decrease of dopamine release from striatum slices seen after alcohol cessation. The inhibition of dopamine release vanishes spontaneously within a few days. Restitution is highly accelerated by piracetam, exhibiting similarities to posthypoxic membrane damages.
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The alcohol preference has been used as a model of drug habituation in animal experiments in order to examine the influence of altered synaptic efficiency of central transmission systems following acute receptor reactions with agonists or antagonists as well as by alterations of receptor sensitivity in mice. Ethanol in 10 per cent solution as the only beverage over 4 weeks produces an ethanol preference quotient 1 in the free choice of ethanol solution and water. Control animals without ethanol exposure before the preference test are only drinking water and refuse ethanol. A single injection of haloperidol increases the preference, apomorphine as well as a long term haloperidol administration producing a dopaminergic supersensitivity diminishes the preference. Moreover the preference is enhanced by atropine, isoprenaline and pholedrine and is decreased by arecoline, propranolol and phenoxybenzamine. Cyproheptadine and picrotoxine do not influence the preference. The results point to a preference promoting influence of the alpha- and beta-adrenergic transmission and to an inhibition by dopaminergic and cholinergic activity. An influence by the 5-HT and GABA system could not be observed. Additionally the paper describes the decrease of the ethanol preference by the nootropics piracetam, meclofenoxane, methylglucamine orotate and nicergoline.
Ethanol interacts with several central transmission systems. Following ethanol application we observed an inhibition of locomotion, vigilance and muscle tone in a modified Irwin-behaviour test. The effect was strengthened by a single dose of haloperidol. Contrary to this observation the ethanol effects decreased when haloperidol was given repeatedly for weeks before the application of ethanol. Three days after haloperidol withdrawal in case of nearly complete haloperidol elimination and development of dopaminergic supersensitivity the decrease was most pronounced. The results indicate that ethanol effects on dopaminergic functions are weakened in consequence of an increased efficiency of the adequate transmission system and vice versa.
The influence of dopaminergic modifiers on morphine-induced analgesia and lethality was studied comparing both the effect of a single pre-dose of haloperidol and and continuous pretreatment for three weeks with haloperidol. A single administration of haloperidol enhanced morphine-induced analgesia probably due to the receptor blocking action of haloperidol which supports the reduction of dopamine release produced by morphine. The daily haloperidol administration for 3 weeks however decreased the analgesic action of morphine in consequence of a dopamine receptor supersensitivity developed in this time. The lethality was increased under both conditions. These results suggest that the dopaminergic system, dependent upon its sensitivity, plays a modulating role in morphine-induced analgesia, but not in morphine-induced lethality.
After withdrawal of daily treatment with haloperidole (2 mg/kg s.c.) and apomorphine (10 mg/kg s.c.) for 21 days, respectively, and clomipramine (15 mg/kg s.c.) for 28 days, a decrease of morphine analgesia is observed. The findings are interpreted as a sensitivity change of the transmission systems involved in the action mechanism of the antinocifensive morphine effect. Morphine lethality remains unaffected by the synaptic efficiency of the transmission systems investigated.
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As revealed in earlier studies, the antinocifensive effect of morphine is brought about, among other things, with involvement of serotoninergic transmission mechanisms. In this context the role of the serotoninergic raphe-hippocampus system has been studied in this paper. Topical microinjections of serotonin into the dorsal hippocampus increased morphine analgesia in a dose-dependent fashion, while application into the striatum had no effect. Morphine injections into the median raphe nucleus in relatively low doses exert an antinocifensive effect which is inhibitable by methysergide. Lysergic acid diethylamide administered into the median raphe nucleus also abolished the effect of morphine in a dose-dependent manner. The results in connection with literature data lend support to the presumed integrative function of the serotoninergic raphe-hippocampus system in the mechanism of antinocifensive action of morphine.
Based on earlier studies that revealed the analogical influence of noradrenaline and serotonin on morphine analgesia and the antinocifensive effect of arecoline, it was tested whether under the influence of dopaminergic substances the inhibition of nocifensive reactions is being altered by arecoline like the action of morphine. In fact, arecoline could be amplified in a dose dependent manner by apomorphine and amphetamine, which alone had no antinocifensive effects. On the other hand, no antagnoism of the dopamine receptor blockers, chloropromazine ahd haloperidole, against arecoline was demonstrable; only the additive effect of apomorphine and amphetamine could be abolished. Therefore it is concluded that dopamine is not directly involved in the spinal mechanism of the antinocifensive effect of central cholinomimetics, but that only supraspinal influences can be varied by the function of dopaminergic neurons.
To stimulation of the Substantia nigra the nucleus caudatoputamen of the rat responds with the release of a short-latent sum action potential that may serve to characterize the interaction between the two nuclear areas. The partly conflicting results reported in the literature about drug effects on this potential prompted us to examine the effectiveness of dopaminergic and cholinergic substances or their antagonists following systematic administration. Chloropromazine increases the amplitude of the potential, while apomorphine has a distinct antagonistic effect. Interesting appear to be the analogical effects of Tricuran, arecoline and apomorphine, and the furtherance of the chloropromazine effect by arecoline.
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Two methods for determining tremors in the rat, acceleration pick-up and electromyogram, including electronic evaluation by impluse rate and frequency are described technically, and the results obtained with either method are compared. Both methods allow quantitative analysis of the drug induced (arecoline) tremor. Electromyographically, the tremor effect can be recorded already after lower doses compared with the electro-mechanical method. Besides, the EMG can be employed on immobilized animals.
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