Effect of diazepam on the gamma motor system indicated by the responses of the muscle spindle of the triceps surae muscle of the decerebrate cat to the muscle stretch

Summary The experiments were performed on 37 intercollicularly decerebrate cats. The triceps surae muscle was subjected to trapezoidal stretches of 10 mm/s or 2 mm/s over a length of 14 mm. The reflex arc was left partially or fully intact. The effect of diazepam given intravenously on the discharge frequencies of group Ia afferent fibres from muscle spindles in the belly of the triceps surae muscle was studied. Diazepam depressed both the dynamic and the static gamma motor responses. When gamma motor fibres were selectively blocked by procaine a parallel shift of the tension-extension curve was observed. From comparison of the effect of procaine and diazepam on the phasic and static responses of the muscle spindle it was concluded that directly after the injection of diazepam the gamma motor activity was completely abolished at a dose as low as 0.1 mg/kg whereas the alpha motor system was only partly depressed even at higher doses. Differences in the effect of diazepam on the dynamic and static gamma system respectively, could not be found.A part of this study was presented at the 9th Congress of the Collegium Internationale Neuropsychopharmacologium, Paris, 1974 (Student and Takano, 1974)     

A comparison of the actions of some drugs on decerebrate rigidity, muscle spindle activity and α-adrenoceptors

1 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)-M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle afferent activity have been studied.2 Methotrimeprazine was eight times as potent as (+)-methotrimeprazine in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity. M & B 18,706 was also eight times as potent as (+)-M & B 18,706 in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity.3 For the above compounds and chlorpromazine there was a significant correlation between the effective doses for the inhibition of the pressor action of noradrenaline and for the reduction of decerebrate rigidity.4 The doses which reduced decerebrate rigidity were similar to those that reduced muscle spindle afferent discharge. It is likely that these drugs reduce decerebrate rigidity by inhibiting fusimotor activity.5 Desipramine increased decerebrate rigidity and increased spindle afferent discharge.6 It is thought that the phenothiazine derivatives studied reduce decerebrate rigidity and spindle afferent discharge by inhibiting receptors for noradrenaline in the central nervous system.     

The effects of Hydergine on acutely denervated cat skeletal muscle vasculature

Summary The effects of Hydergine on the resistance, capacitance and precapillary sphincter vessels have been studied in cat calf muscle.Hydergine possesses a unique vascular profile: it causes dose-dependent constriction of the capacitance vessels, dose-dependent dilation of the pre-capillary sphincter vessels without significantly altering the tone of the resistance vessels.     

Effect of opiates on the caudate spindle in the cat

The effect of opiate drugs on the caudate spindle (CS) in the cat was observed following both systemic and intracaudal administration. Systemic administration of morphine, pentazocine and pethidine inhibited the CS. The inhibitory effects of opiates were antagonized by lysergide and methysergide but not by naloxone, chlorpromazine, dehydrobenzperidol, amphetamine and atropine. Contrary to their systemic administration, the investigated opiates morphine, pentazocine, pethidine and Met5-Enkephaline enhanced the CS, when injected into the caudate nucleus close to the site of stimulation. Those facilitating effects of opiates on the CS were completely blocked by naloxone. The results suggest that serotoninergic mechanisms might be involved in the action of opiates on the neuronal activity of the caudate nucleus.     

Dantrolene effects on neuromuscular function in cat soleus muscle.

Dantrolene sodium (DS) was investigated for its effects on cat soleus muscle contractile properties and motor nerve terminal activity in particular. DS, 0.1-1.5 mg/kg i.v., caused a dose-dependent depression of indirectly elicited contractile strength which was more pronounced at lower frequencies of stimulation. Maximum tetanic strength at frequencies of 10-400 Hz was depressed to a lesser degree than contractile responses evoked by lower frequencies of stimulation; the twitch/tetanus contraction ratios were reduced with increasing dose, primarily because of diminished twitch. DS was without effect on motor nerve terminals as evidenced by normal post-tetanic repetition in the nerves following DS administration. Post-tetanic potentiation became relatively larger in amplitude as contractile strength was diminished. These data suggest that DS depresses neuromuscular function at a site other than the neural apparatus at the neuromuscular junction.     

Depressant effects of phenoxygenzamine on potassium contracture in cat ventricular muscle

Phenoxybenzamine has been shown to have a depressant action on K+-depolarization contracture in cat ventricular muscle. In the present study, we show that this depressant action is specific for phenoxybenzamine and occurs in the presence of beta-adrenergic receptor blockade with nadolol. K+-contracture is not depressed by phentolamine nor augmented by phenylephrine. Thus, the depressant action of phenoxybenzamine is not mediated by its effects on cardiac adrenergic receptors.     

The effects of hornet venom sac extract on the electrical activity of the cat brain

A method for testing minute quantities of extracts of hornet venom sacs by injection into the vertebral artery of cats is described. Neurotoxic effects of venom sacs manifested by isoelectric EEG and by depression of respiratory centre, appeared prior to cardiovascular manifestations. Injection into the carotid artery necessitated 100 times large amounts of venom and a longer time elapsed before results similar to those after intravertebral injection were obtained. The cardiovascular manifestations preceded the cerebral effect using intracarotid injection. The active fraction seems to be proteinaceous, has antigenic properties and does not cross a dialysis membrane. Incubation of venom with antivenin serum prepared by immunization of a goat caused inactivation of the neurotoxic and hemolytic effects of the venom sac extract.     

The effects of trimethadione on pentetrazol-induced discharges of primary muscle spindle afferents from the hind limb of the rat

1 Recordings have been made from primary muscle spindle afferents in split dorsal root filaments of rats anaesthetized with urethane. 2 Injection of pentetrazol (PTZ, 10 mg/kg) produced elevated discharge in the afferents with intact efferents without any charge in tension or electrical activity of the muscle of origin. 3 This elevated discharge was found to contain elements of both gamma d and gamma s activation. 4 Trimethadione (100 mg/kg), itself produced a transient increase in discharge and effectively suppressed PTZ-induced discharges of the afferents for at least 2 h. 5 These results are discussed in the context of established effects on sensory and motor systems.     

The effects of angiotensin I and angiotensin II on the isolated tracheal muscle of the cat.

The effects of Asp1-beta-amide-Val5-angiotensin II (A II) and Asp1-Ile5-angiotensin I (A I) have been studied on the isolated continuously superfused cat tracheal muscle contracted by 5-hydroxytryptamine (5-HT). Both peptides have been shown to induce dose-dependent relaxation on this muscle. Similar effects have been obtained with synthetic bradykinin, prostaglandin E2 (PGE2), noradrenaline and histamine. The effects of bradykinin, A I and A II have been shown to be inhibited by aspirin but not by propranolol, metiamide, SC 19220 or a specific, competitive antagonist of A II. The relaxing effect of A I is not due to the conversion of decapeptide to octapeptide A II. The possible mechanism of the relaxing effects of A I and A II on the cat isolated tracheal muscle is discussed.     

The effects of atenolol on spontaneous and reflex activity of the sympathetic nerves in the anaesthetized cat.

1 The reduction in the sympathetic efferent discharge observed after propranolol may be due to either a central or a peripheral effect. The beta-adrenoceptor blocking drug, atenolol, is not thought to enter the brain and therefore any reduction in the level of sympathetic efferent discharge observed after atenolol is likely to be mediated peripherally rather than centrally. 2 Cats were anaesthetized with alpha-chloralose and artificially ventilated and a number of variables known to affect the sympathetic nerves were monitored throughout the experiment and maintained within normal limits. Recordings were made from few fibre preparations from the lumber trunk and the renal nerves. Blood pressure was either raised or lowered by the injection of phenylephrine (1-4 microgram/kg) or glyceryl trinitrate (2-20 microgram/kg) and the sympathetic efferent discharge was recorded over a range of blood pressures when the blood pressure was steady. 3 Thirty min after giving atenolol (3 mg/kg) the blood pressure, heart rate and sympathetic efferent discharge were significantly reduced. Atenolol also attenuated the reflex responses of the sympathetic nerves to changes in the blood pressure. 4 It is suggested tht atenolol has its actions on sympathetic nerves at a site outside the CNS and some possible mechanisms are discussed.     

Anticonvulsant modification of tripelennamine effects on the electrographic activity of the cat brain

The modification of tripelennamine effects on the electrographic activity of cat brain by pretreatment with phenobarbital, trimethadione, diphenylhydantoin or saline was examined with the aid of power spectral density analysis. Only phenobarbital and trimethadione pretreatments effectively increased the tripelennamine dose required for induction of paroxysmal activity. Diphenylhydantoin and phenobarbital pretreatments resulted in greater cortical amplitude increases during tripelennamine infusions, reaching mean normalized power values of 520 and 330%, respectively, just prior to paroxysm. With trimethadione pretreatment marked power changes were not induced during the tripelennamine infusion although more sharp wave activity was noted than was seen with saline pretreatment. Tripelennamine-induced hippocampal power changes were minimal except with diphenylhydantoin pretreatment, reaching 190% just prior to paroxysm. Dominant hippocampal 4.0–4.5 Hz activity, which was induced by tripelennamine with saline pretreatment, was reduced or eliminated with all anticonvulsant pretreatments. The findings indicate that the previously suggested role of hippocampal theta activity in the production of tripelennamine-induced paroxysmal activity is abolished by anticonvulsant pretreatment. The cerebral cortex appears to play a primary role in the production of epileptiform activity by tripelennamine in the presence of anticonvulsants.     

Effect of substance P and Met-Enkephalin on cat colonic smooth muscle activity

• 1.1. The effects of substance P (2.5×10⁻⁸ M) (SP) and met-enkephalin (10⁻⁷ M) (ME), when administered alone or in combination (SP+ME), on the contractile activity of cat colonic muscle strips were compared.
• 2.2. SP evoked powerful contractions of the circular muscle strips (2.30±0.36 g) (background 0.65±0.10 g).
• 3.3. In the majority of cases, ME significantly increased the background activity (1.88±0.34 g and 0.70±0.10 g, respectively).
• 4.4. The two substances administered together produced the most pronounced contractile activity (3.86±0.44 g).
• 5.5. The longitudinal muscle strips showed higher spontaneous and evoked contractions.
• 6.6. Thus ME contributes to the increase in the effect of SP on colonic contractile activity.

     

布比卡因对肌梭的损害作用

用 54只健康成年家兔 ,观察肌注布比卡因对腓肠肌肌梭的作用。组织学结果显示 ,肌注布比卡因后12 h,肌梭即可出现轻度的变性 ;2～ 3d受损最严重 ,可出现肌梭的广泛坏死 ;1周后受损肌梭可自行修复改善 ,至 3周末可完全修复正常。提示布比卡因能引起肌梭发生可逆性的变性及坏死改变。     

The influence of GABAergic drugs on PGO activity in the cat

The effects of drugs modifying GABAergic neurotransmission have been examined on ponto-geniculo-occipital (PGO) waves induced in the encéphale isolé cat by reserpine (PGOres), Ro4-1284 (PGO1284) or PCPA (PGOPCPA). The GABA agonists muscimol and THIP both caused large increases in density of PGOPCPA. The PGO1284 and PGOres were less affected although, of these, a larger increase in PGO1284 density was recorded. None of the increases could be reversed by subsequent injection of bicuculline. Chlordiazepoxide brought about large increases in PGOPCPA density but was ineffective in altering PGOres or PGO1284. The GABA transaminase inhibitor gamma-acetylenic GABA increased the density of all PGO waves but was not effective in the case of PGOPCPA. These results confirm a role for GABA in modulating PGO activity. The pathways involved in this GABA modulation are discussed.     

Implications of altered inotropic effects of phenylephrine in pressure-overloaded cat ventricular muscle

The positive inotropic action of phenylephrine in cardiac muscle is mediated by alpha- and beta-adrenoceptors. Data suggest the responsiveness of myocardium to inotropic agents is altered in cardiac disease. We evaluated the actions of phenylephrine on isometric contraction and K+-induced contracture in isolated cat right ventricular muscle from normal hearts and hearts with partial pulmonary artery ligation-induced pressure overload of 5-11 days in duration. Peak contractile force (Po) and rate of force development (dP/dt) were lower (p less than or equal to 0.005) in pressure-overloaded (0.59 +/- 0.2 g/mm2 and 4.6 +/- 1.7 g/s/mm2, respectively) than in normal (1.33 +/- 0.2 g/mm2 and 10.5 +/- 1.6 g/s/mm2, respectively) muscle. Phenylephrine (10(-6), 5 X 10(-6), and 10(-5) M) significantly (p less than or equal to 0.01) increased Po and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 X 10(-6) M) reduced peak K+-induced contracture force (Pc) similarly in normal (-30 +/- 8%) and pressure-overloaded (-36 +/- 11%) muscles. beta-Adrenergic blockade (nadolol, 10(-4) M) reduced, but did not abolish, the "relaxant" action of the drug on Pc in both muscle groups. The lack of a positive inotropic effect of phenylephrine in pressure-overloaded muscle suggests a derangement in both alpha- and beta-adrenoceptor function in this model of cardiac disease.