Attrition of the Zeigarnik effect: role of subjects' expectancy aroused by placebos.

The present paper describes the effect for 45 medical students and interns of "placebo" treatment on the Zeigarnik effect. Attrition of the Zeigarnik effect caused by placebo was resistant to caffeine and diazepam (ns = 58 and 28).

Some aspects of activity profile of sodium lawsonate in mice and rats.

Sodium lawsonate (SL: derivative of lawsone, hydroxy-1,4-naphthaquinone) was studied for its activity profile in mice and rats, with emphasis on actions on the central nervous system. The drug produced a cataleptic state, hypothermia and loss of active avoidance behaviour, but it did not augment barbiturate sleep. The catalepsy was prevented by hyoscine (mice) or by sodium salicylate (rats). SL did not affect apomorphine-sterotypy (a dopamine-mediated behaviour) but blocked the lithium-induced head twitches (a serotonin-mediated behavioural response). SL did not produce excitation, analgesia or exhibit anti-MES activity. All actions of SL were rapid in onset and brief in duration. In view of effective dose range (40-80 mg/kg, i.p.) and MLD 50 values (76 mg/kg, i.p., in mice; 122 mg/kg, i.p., in rats), safety index of SL appears to be low.

The effect of centrophenoxine at the skeletal neuromuscular junction.

Centrophenoxine exhibited some interesting actions at the neuromuscular junction. The drug was ineffective in rat or chick preparations, but blocked neuromuscular transmission in frog preparations. The blockade was reversed by adrenaline, potassium, choline and physostigmine. The drug had no effect on muscle contractility or endplate cholinoceptor. Hemicholinium 3 induced a neuromuscular blockade in rat (in vivo) which was reversed by choline but not by centrophenoxine. Neither of these two drugs could reverse the blocking effect of hemicholinium in frog preparations. It is concluded that centrophenoxine acts only in frog and the blockade involves a presynaptic mechanism. The work further suggests that choline uptake systems in the rat and the frog may not be identical, since choline competed with hemicholinium for the uptake system in rat and with centrophenoxine (but not with hemicholinium) in the frog.

The effect of estradiol on the alterations in monoamine-mediated behavioural responses induced by administration of electroconvulsive shocks or imipramine to female rats.

Female rats were treated daily with electroconvulsive shocks (ECS) or imipramine (10 mg/kg) for 10 days. Both types of treatment enhanced behavioural responses mediated by 5-hydroxytryptamine (5-HT) and noradrenaline (NA). A behavioural response mediated by dopamine (DA) was enhanced by electroconvulsive shock-treatment alone. On the other hand, rats treated only once with imipramine exhibited reduced DA-mediated behaviour. Priming the rats with estradiol valerate before starting electroconvulsive shock- or imipramine- treatment did not produce any significant effect on the enhancement in the behavioural response mediated by 5-HT. The enhancement in behaviour mediated by NA caused by electroconvulsive shock was also not altered, but that caused by treatment with imipramine was abolished. Enhancement of behaviour mediated by DA following electroconvulsive shock-treatment was also attenuated, while there was a positive reduction in behaviour mediated by DA in imipramine-treated rats. The two therapeutic approaches to depression, viz., electroconvulsive shock and imipramine, thus produced somewhat different effects on the central functions mediated by monoamines. Furthermore, an estrogen given prior to the treatments differentially altered the influence exerted by electroconvulsive shock and imipramine on monoamine functions in brain. The results may be pertinent to the clinical impression that estrogens produce a partial resistance to the antidepressant efficacy of imipramine-like drugs.

The effect of some anti-epilepsy drugs on enhancement of the monoamine-mediated behavioural responses following the administration of electroconvulsive shocks to rats.

Daily administration of electroconvulsive shocks (ECS) to rats for 10 days resulted in enhanced 5-hydroxytryptamine (5-HT), dopamine (DA) and noradrenaline (NA)-mediated behavioural responses. 5-HT and NA-mediated responses were still enhanced after 21 shock-free days. The three types of behavioural responses were also studied in rats given phenytoin sodium, carbamazepine and diazepam every day, alone, or 1 h after ECS administration. Phenytoin did not alter the ECS-induced enhancement of any of the three behaviours. Carbamazepine and diazepam significantly retarded the enhancement in 5-HT and DA-mediated behaviours, although they did not alter the enhancement in NA-mediated behaviour.

Effect of guanethidine on alpha-adrenoceptor blocking potency of phentolamine in vitro.

The effect of guanethidine on the alpha-adrenoceptor blocking potency of phentolamine was studied using the rabbit aortic strip and rat vas deferens. The agonists used were noradrenaline (in presence of DOCA and cocaine which block uptake mechanisms) and xylometazoline (which is not taken up by uptake mechanisms). Guanethidine augmented the responses to noradrenaline and xylometazoline and increased the pA2 value of phentolamine against both agonists. Increased affinity of alpha-receptors may be partly responsible for the guanethidine-induced supersensitivity to alpha-adrenoceptor agonists.

Biting activity by Aedes egypti mosquitoes in guinea-pigs. An experimental model for screening the effect of some systemically administered compounds.

The Aedes egypti mosquito fed consistently on guinea-pigs in a 2-hour period (n = 61), the mean percent feeding rate (+/- S.D.) being 88.84 +/- 9.32. Of a total of 34 different compounds systematally administered in guinea-pigs and tested for their effect on the mosquito biting rate using the above model, five: heparin, sodium fluoride, aminocaproic acid, thiourea and dithiocarb partially reduced the biting rate. The results are consistent with the view that certain aminoacids or proteins of blood or tissues serve as 'pheromones' attracting the mosquito to guinea-pigs.

Characterization of ultraviolet light-induced relaxation of the isolated duodenum of the rat.

1 Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation. 2 The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences. 3 Changes in the ionic environment of the tissue showed that NA+ and Ca2+ were essential for the photorelaxation. K+ depolarized-tissue did not show the photoresponse. 4 The presence of the metabolic inhibitors, iodoacetic acid, 2,4-dinitrophenol, sodium fluoride, sodium azide or potassium cyanide, abolished the photorelaxation response. 5 It is proposed that the photorelaxation of the tissue resulted from the liberation of metabolic energy following NO2 ion-dependent absorption of u.v. light energy, which in turn, interfered with the Na+ ion movement across the cell membrane.

Antagonism by some beta-adrenoceptor-blocking agents to cholinergic stimulation of skeletal muscle in vitro.

Antiacetylcholine activity some beta-adrenoceptor-blocking drugs was investigated using isolated guinea pig cremaster muscle and frog fectus abdominis muscle. On the cremaster muscle, the antagonism to acetylcholine was non competitive in K0 1313, (+/-)-INPEA and (--)-INPEA, competitive in (+)-INPEA and functional in practolol; All three INPEA isomers, practolol and propranolol behaved as noncompetitive antagonists of acetylcholine on frog rectus muscle. Caffeine-induced contractions of this muscle were partially inhibited by propranolol but not by the other drugs. It is suggested that the beta-adrenoceptor-blocking drugs produce their antiacetylcholine action by interaction with sites on the muscle which are different from the cholinceptor, and which vary between compounds and species.

Some photoresponses of isolated tissue preparations to ultraviolet light in the presence of photosensitizers.

Responses of isolated tissue preparations to ultraviolet (UV) light were studied with and without the presence of photosensitizers like eosin, fluorescein and sodium nitrite. Exposure to UV light in the presence of sodium nitrite induced consistent relaxation of rat duodenum. The photorelaxation was found to be related to the concentration of sodium nitrite. Adrenergic or cholinergic mechanisms do not seem to be involved. The isolated rat duodenum preparation exhibited quantitatively consistent photoresponse for 3 to 4 hr at its normal tone obviating the need for additional spasmogens as needed with other preparations. The preparation is a suitable test model for the study of photobiologic response evoked by UV light.

Characterization of the adrenoceptor in the isolated cremaster muscle of the guinea-pig.

1 Contractions of the isolated cremaster muscle of the guinea-pig obtained in response to direct electrical stimulation were augmented by salbutamol, isoprenaline, adrenaline, noradrenaline and orciprenaline (in that order of potency), and by potassium chloride. Phenylephrine and xylometazoline had no effect. 2 The augmenting effect of isoprenaline on the twitch response was not altered by yohimbine or tolazoline, but was totally prevented by butoxamine, (--)-1-(4-nitrophenyl)-2-isopropylamino-ethanol (INPEA), (+/-)-INPEA, sotalol, metalol and practolol; (+)-INPEA was much less effective. The augmenting effect of potassium was not altered by beta-adrenoceptor blockade. 3 The results are consistent with the view that the augmenting effect of the sympathomimetic agents is mediated through beta2-type of adrenoceptor in the skeletal muscle fibres.

The isolated cremaster muscle preparation and (external) spermatic nerve-cremaster muscle preparation of the guinea-pig.

The isolated cremaster muscle preparation and spermatic nerve-cremaster muscle preparation of the guinea-pig were studied in vitro to determine their suitability as pharmacological test models. The preparation was contracted by acetylcholine, carbachol, succinylcholine and decamethonium (pD2 values, 4-2, 5-3, 7-3 and 7-4, respectively) through an action on a curare-sensitive cholinoceptor. Lobeline and DMPP were ineffective. Nicotine contracted the muscle, but there was tachyphylaxis. Tubocurarine and hexamethonium presumably competitively antagonized acetylcholine (pA2 values, 7-3 and 5-8); lobeline was a non-competitive antagonist (pD'2 value, 6-4). Atropine and mecamylamine exerted a dualistic action against acetylcholine (final pD'2 values, 5-3 and 6-7, respectively). Tubocurarine, succinylcholine and decamethonium exhibited their typical action when tested with spermatic nerve-cremaster muscle preparation; the latter two drugs also produced muscle spasm. Hexamethonium was a weak blocker of neuromuscular transmission. Atropine, mecamylamine, lobeline and DMPP exhibited neuromuscular blocking activity; however, directly evoked muscle twitches were also notably affected. The cremaster muscle preparations seem to add usefully to the list of currently used in vitro tests, with the added advantage that a mammalian skeletal muscle model is used for simultaneous quantitative studies.

A study of some beta-adrenoceptor blocking agents on skeletal muscle.

The effect of three recently introduced beta-adrenoceptor blockers practolol, USVC 6524 and Inpea was studied on various skeletal muscle preparations. Practoloo, USVC 6524 and Inpea produced a dose related inhibition of acetylcholine induced contractions of rectus abdominis muscle of frog. These drugs also blocked neuromuscular transmission when tested on in vitro rat phrenic nerve diaphragm preparation; the blockade was partially reversed by physotigmine, KCl and adrenaline and was potentiated by d-tubocurarine. In gastrocnemius sciatic muscle-nerve preparation only Inpea exhibited neuromuscular blocking activity, while practolol and USVC 6524 did not show any effect up to a dose of 10 mg/kg (intraarterially). The apparent discrepancies between the results of in vitro and in vivo experiments could not be adequately explained. It has been discussed that the neuromuscular blockade caused by presently investigated beta-adrenoceptor blocking agents is essentially due to curare-like activity and to a small extent may be due to local anaesthetic activity.

Effect of drugs on rat paw oedema induced by mercury.

1 Metallic mercury (0.04 ml) injected into the foot pad of rats induced a consistent inflammatory reaction, which at 4 h showed oedema but no cellular infiltration or vascular changes. The lesions exhibited lymphocytic infiltration, vasodilatation and haemorrhages at 24 and 48 h, and often became cystic after 2-3 weeks, before healing. The oedema volume at 4 h was used to test anti-inflammatory activity of drugs.2 Cortisone, phenylbutazone, indomethacin, acetylsalicylic acid, flufenamic acid and propranolol exhibited potent, dose-related anti-inflammatory activity. Aminopyrine, chloroquine and chlorpromazine were only moderately effective. Dimercaprol, adrenaline, and to some extent, mepyramine also inhibited mercury-induced oedema.3 This simple model of acute inflammation may be useful for preliminary tests of anti-inflammatory activity.