International journal of neuropharmacology最新文献

Rats pretrained in ago-nogo avoidance discrimination were treated daily with 1mgkg of scopolamine HBr s.c. 40 min before testing sessions. EEG records were taken twice a week, before and after sessions. The drug caused initially a disruption in performance and EEG synchronization. Upon repeated exposure the behavioural deficit was progressively compensated for, while the EEG alteration persisted. The administration of physostigmine (1mgkg s.c.) to desensitized scopolamine-treated animals provoked a disruption in the performance and an EEG desynchronization. Repeated exposure to scopolamine and physostigmine led to a rapid behavioural desensitization to the combined treatment.

Effects of 5-hydroxytryptamine (5-HT), lysergic acid diethylamide (LSD) and other psychotomimetics upon the potentials induced in thin sections from the superior colliculus of the guinea pig were studiedin vitro. The postsynaptic field potential (PSR) evoked by optic tract stimulation was suppressed by 5-HT in concentrations of 10⁻⁷–10⁻⁶M. Single neuron discharges induced by optic tract stimulation were also suppressed by 5-HT but spontaneous cell firings were not affected. By higher concentrations of 5-HT (more than 10⁻⁴M) PSR was once suppressed but gradually recovered. LSD, lysergic acid ethylamide (LAE) and other related compounds potentiated the 5-HT suppressing action in relatively low concentrations but blocked it in higher ones. Morphine and 2-bromolysergic acid ethylamide (BOL) did not antagonize the 5-HT action. When two shocks were delivered to the optic tract at short intervals and the time course of suppression of the second PSR was studied, it was found that LSD and related compounds accelerated the recovery of the test PSR. Physiological roles of 5-HT in the superior colliculus are discussed.

Adrenaline (10–200 μg) and noradrenaline (50 μg) when injected into the lateral cerebral ventricle of pentobarbital-anesthetized rabbits produced a fall in systemic blood pressure, a decrease in spontaneous heart rate and a stimulation of spontaneous respiration. Isoproterenol (50–200 μg) caused a fall in blood pressure and an acceleration of heart rate, whereas phenylephrine (200 μg) caused a slight rise in blood pressure in association with a decrease in heart rate. The hypotension and bradycardia induced by adrenaline were not significantly affected by bilateral vagotomy. Pretreatment of rabbits with intravenous reserpine reversed the adrenaline-induced hypotension to a hypertension and abolished the bradycardia induced, but did not affect the respiratory stimulation. The cardiovascular responses to intraventricular adrenaline were abolished by transection of the spinal cord. In unanesthetized rabbits adrenaline produced presser and cardio-stimulatory effects followed by depressor and cardio-inhibitory effects. These findings would suggest a centrally mediated hypotensive action of adrenaline in anesthetized rabbits but a hypertensive action in unanesthetized rabbits. Furthermore, changes in the cardiac function might be associated with changes in local blood flow, as postulated byKanekoet al. (1960).

Biogenic amines and related compounds, and certain amino acids were applied by microelectrophoresis onto single red nucleus neurons. The cats were either lightly anesthetized or specially prepared in the unanesthetized state.l-Glutamic anddl-homoeysteic acids were potent excitants while gamma-aminobutyric acid was a strong depressant of neuronal activity. Acetylcholine and carbamylcholine, 5-hydroxytryptamine and lysergic acid diethylamide, noradrenaline and dopamine and other phenylethylamines stopped brachio-rubral synaptic transmission, reduced “spontaneous” firing and amino-acid evoked firing of RN neurons. Parenterally administered drugs which disturb motor coordination, such as lysergic acid diethylamide, bufotenine and mephenesin depress directly or indirectly rubral neuronal activity. 4-Methoxyphenylethylamine when applied locally did depress rubral neurons. However, when applied intravenously 4-methoxyphenylethylamine caused a hypokinetic rigid syndrome to develop; parallel to the increases in muscle tension and electromyogram activity were increases in rubral neuronal firing. The evidence presented and from a Preliminary Note (H. McLennan) indicates that the transmitter released from the brachium fibers to excite rubral neurons is not acetylcholine. The rubro-cerebellar fibers may be cholinergic.

The characteristics of nerve endings present in the vas deferens and in the seminal vesicle of guinea pig have been studied by pharmacological techniques and by electron microscopy. From a pharmacological point of view it appears that cholinesterase inhibitors potentiated in both organs the contractions elicited by stimulation of the hypogastric nerve. This potentiation is present even in preparations obtained from animals pretreated with reserpine or α-methyltyrosine and is prevented or abolished by atropine. On the basis of the electron microscopic studies two types of nerve terminals, adrenergic and cholinergic, can be distinguished. The difference between the two types of nerve endings is still more evident in the organs of animals pretreated with iproniazid and DOPA. These results are interpreted as supporting the concept that the hypogastric nerve carries, to the vas deferens and to the seminal vesicle, fibers of adrenergic and cholinergic type.

Dose-response curves for the prevention of tetrabenazine-induced ptosis in mice by antihistamines such as dexchlorpheniramine, are shifted to the right in parallel fashion by raising the dose of tetrabenazine, whereas the dose-response curves for imipramine-like antidepressants are relatively unaffected. Another difference between dexchlorpheniramine and imipramine is that the antihistamine reverses α-methyl-tyrosine-induced ptosis whereas imipramine is ineffective. In both procedures, methamphetamine produces effects similar to dexchlorpheniramine, suggesting that dexchlorpheniramine has a central sympathomimetic effect. Additional evidence for this hypothesis is that dexchlorpheniramine-indueed lethality is enhanced by aggregation (ten mice per cage vs. five mice per cage) and that this aggregate lethality can be prevented by phenoxybenzamine but not by α-methyl-tyrosine. The central sympathomimetic effect of dexchlorpheniramine may be similar to the direct effect of methamphetamine, which has been demonstrated in the present studies by reversal of both tetrabenazine- and α-methyl-tyrosine-induced ptosis. The present studies have not ruled out the possibility that antihistamines such as dexchlorpheniramine can antagonize ptosis in part by inhibition of norepinephrine uptake.

When ACh or carbachol was directly applied to the isolated amphibian spinal cord, a slow depolarization which originated at or near the dorsal root nerve terminals could be recorded by means of the sucrose-gap method. This depolarization was a transient phenomenon. A marked and transient decrease in the amplitude of the DR-DRP was observed during the development of the ACh depolarization. With relatively small concentrations of ACh, the reduced amplitude of the DR-DRP was gradually restored to an almost normal value within 30–40 min. The depolarization of the dorsal root nerve terminals as well as the reduction in the size of the DR-DRP, caused by ACh or carbachol, were enhanced by anti-AChE's and prevented by atropine, DHE, d-TC or nicotine. These pharmacological properties were similar to those of the VR-DRP. On the basis of the experimental observations, the possible location of the cholinoceptive receptor sites in the amphibian spinal cord was discussed.

Efferent neural traffic over filaments from the cervical and thoracic vagi, and over postganglionic filaments emerging from the stellate ganglion, was studied in cats subjected to progressive, fatal intoxication with digitoxin or ouabain. Vagal efferent activity was increased by glycoside administration in 71% of trials. Depression was never observed. No specific effect on sympathetic activity was noted prior to the onset of cardiac arrhythmia. In the later stages of glycoside intoxication, however, enhancement of sympathetic activity was uniformly observed. Except as an almost terminal event, neither vagal nor sympathetic activity was consistently related to heart rate or level of systemic blood pressure. A reciprocal relationship between the two autonomic systems was not revealed.

The volume of water consumed in a 60 min period by rats deprived of water for 23 hr was significantly reduced by administration of tertiary amine cholinergic blocking agents such as atropine, homatropine or scopolamine, or by administration of their quaternary N-methyl derivatives. Dose-response curves for the tertiary amines were mutually parallel and showed a potency order of scopolamine>atropine>homatropine. Dose-response curves for the quaternary compounds were not parallel. The effect of methylatropine on thirst-induced water consumption showed a significant carryover effect on the post-drug day. Reduction of thirst-induced drinking could also be achieved by administration of acetylcholinesterase inhibitors such as physostigmine and neostigmine. The results presented infer the presence of a peripheral cholinergic component in thirst-induced water consumption.