Analeptic effects of aranthol in vasomotor depression induced by quinidine.
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The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 micrograms) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0-5.0 micrograms), RX 77368 (0.1-1.0 microgram) and CG 3509 (0.1-1.0 microgram) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 micrograms) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 microgram) and RX 77368 (0.1 microgram) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20-100 micrograms) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.
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Cocaine (1-5 mg/kg, IV) shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was completely blocked by scopolamine (1 mg/kg, IV), but not by scopolamine methylbromide, suggesting that a central cholinergic mechanism was involved. In urethane-anesthetized rats cocaine (1 mg/kg, IV) consistently generated hippocampal EEG theta rhythm lasting about 40 min. This effect was also abolished by scopolamine. These results suggest that cocaine produced behavioral and EEG arousal responses that involved the septohippocampal cholinergic system.
A method for the perfusion of the isolated brain of the rat with synthetic fluorocarbon emulsion is described. The functional states of the brains were investigated using biochemical, biophysical, and histological methods. After 4.5 h of perfusion, all brains were in excellent condition and comparable to the in vivo state. The influence of perfusion conditions on the viability of the brains was studied. Deep hypothermia was well tolerated; at 13 degrees the EEG exhibited a mean frequency of about 8 Hz, while the mean amplitude was about 40% lower than at 28 degrees or 36 degrees. Constant-pressure perfusion did not affect brain function, provided that the pressure amplitude was very slowly decreased. During application of pentylenetetrazole (PTZ) it was found that the threshold concentration of PTZ in the perfusion medium to induce epileptic seizure discharges was 0.13 mg/ml. However, after repeated application of PTZ, the threshold concentration decreased exponentially, indicating a kindling phenomenon. It could be shown that not PTZ as such, but the spike potentials provoked by PTZ, induced the kindling effect. This was inhibited by application of primidone or phenobarbital.
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