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).

Characterization of norepinephrine accumulation by a crude synaptosomal-mitochondrial fraction isolated from rat heart.

Norepinephrine (NE) uptake into a heart synaptosomal-mitochondrial fraction was assessed under conditions where neuronal uptake (type 1) was linear with respect to both time and protein concentration. The NE accumulation process was sensitive to incubation temperature, sodium ion concentration and medium osmolality. Furthermore, NE uptake was attenuated by the neuronal uptake inhibitor desmethylimipramine (DMI) in a concentration dependent manner; the IC50 value was approximately 10 nM and maximum inhibition was obtained at 100 nM. In contrast, the extraneuronal uptake inhibitor, metanephrine did not significantly attenuate NE uptake. Kinetic analysis demonstrated that the DMI sensitive NE accumulation is saturable with a KM of approximately 400 nM and that NE uptake occurs via a single uptake process. This demonstration of neuronal type NE uptake by a synaptosomal-mitochondrial fraction constitutes a successful demonstration of the preparation of a rat heart subcellular fraction containing functional synaptosomes.

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.

Antagonism of some central effects of d-tubocurarine by gamma-aminobutyric acid.

d-Tubocurarine (dtc) administered intracerebroventricularly (icv) to rats produced seizures. Gamma-aminobutyric acid (GABA) administered icv or hydroxylamine administered intraperitoneally (ip) protected the rats from dtc-induced seizures. GABA administered (ip) was ineffective. Local application of dtc to the spinal cord in decerebrate dogs produced facilitation of the scratch reflex. Application of GABA to the spinal cord inhibition the scratch reflex. It is thus concluded that the excitatory effects of dtc on the CNS may be through inhibition of naturally occurring inhibitory substances such as GABA or a closely related compound.

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.