The actions of three diaminopyridines on the chick biventer cervicis muscle.

The effects of 2,3-, 2,6- and 3,4-diaminopyridine were investigated on the isolated chick biventer cervicis muscle preparation. All three compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated preparations. Less twitch augmentation was observed in directly stimulated preparations. 3,4-Diaminopyridine was the most effective of the compounds in facilitating neuromuscular transmission, but exhibited less convulsant activity than 4-aminopyridine. 3,4- and 2,3-diaminopyridine in high concentrations caused contractures that were inhibited by erabutoxin b or by beta-bungarotoxin. It is suggested that the diaminopyridines increase both evoked and spontaneous acetylcholine release.     

The actions of aminopyridines on avian muscle

Summary The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle. All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release.     

The actions of 5-hydroxytryptamine on isolated skeletal muscle preparations.

The effects of 5-hydroxytryptamine (5HT) on the mouse phrenic nerve--hemidiaphragm and frog sartorius muscle preparations were studied using twitch tension and intracellular recording methods. Between 1--7.5 mM 5HT transiently augmented the twitch response of the diaphragm to indirect, but not direct, stimulation. Above 5 mM 5HT the augmentation was followed by a concentration-dependent twitch blockade. The blockade was more apparent in anticholinesterase-treated preparations, and was seen to a lesser extent in directly stimulated muscles. Intracellular recording from diaphragm muscles revealed that 5HT depressed the amplitudes of both miniature endplate potentials (m.e.p.p.s.) and endplate potentials (e.p.p.s.), this effect being more pronounced in the presence of neostigmine. 5HT also greatly prolonged the duration of the e.p.p.s. In the sartorius muscles, 1--5 mM 5HT slowed and depressed action potentials. It is suggested that 5HT facilitates transmission by an anticholinesterase action and inhibits by blockade of receptor ion channels.     

In vitro neuromuscular activity of 'colubrid' venoms: clinical and evolutionary implications.

In this study, venoms from species in the Colubrinae, Homalopsinae, Natricinae, Pseudoxyrhophiinae and Psammophiinae snake families were assayed for activity in the chick biventer cervicis skeletal nerve muscle preparation. Boiga dendrophila, Boiga cynodon, Boiga dendrophila gemincincta, Boiga drapiezii, Boiga irregularis, Boiga nigriceps and Telescopus dhara venoms (10 microg/ml) displayed postsynaptic neuromuscular activity as evidenced by inhibition of indirect (0.1 Hz, 0.2 ms, supramaximal V) twitches. Neostigmine (5 microM) reversed the inhibition caused by B. cynodon venom (10 microg/ml) while the inhibitory effects of Psammophis mossambicus venom (10 microg/ml) spontaneously reversed, indicating a reversible mode of action for both venoms. Trimorphodon biscutatus (10 microg/ml) displayed irreversible presynaptic neurotoxic activity. Detectable levels of phospholipase A2 activity were found only in T. biscutatus, T. dhara and P. mossambicus venoms. The results demonstrate a hitherto unsuspected diversity of pharmacological actions in all lineages which may have implications ranging from clinical management of envenomings to venom evolution.     

Modulation of intracellular Ca2+ levels by Scorpaenidae venoms.

The crude venoms of the soldierfish (Gymnapistes marmoratus), the lionfish (Pterois volitans) and the stonefish (Synanceia trachynis) display pronounced neuromuscular activity. Since [Ca(2+)](i) is a key regulator in many aspects of neuromuscular function we sought to determine its involvement in the neuromuscular actions of the venoms. In the chick biventer cervicis muscle, all three venoms produced a sustained contraction (approx 20-30% of 1mM acetylcholine). Blockade of nicotinic receptors with tubocurarine (10 micro M) failed to attenuate the contractile response to either G. marmoratus venom or P. volitans venom, but produced slight inhibition of the response to S. trachynis venom. All three venoms produced a rise in intracellular Ca(2+) (approx. 200-300% of basal) in cultured murine cortical neurons. The Ca(2+)-channel blockers omega-conotoxin MVIIC, omega-conotoxin GVIA, omega-agatoxin IVa and nifedipine (each at 1 micro M) potentiated the increase in [Ca(2+)](i) in response to G. marmoratus venom and P. volitans venom, while attenuating the response to S. trachynis venom. Removal of extracellular Ca(2+), replacement of Ca(2+) with La(3+) (0.5mM), or addition of stonefish antivenom (3units/ml) inhibited both the venom-induced increase in [Ca(2+)](i) in cultured neurones and contraction in chick biventer cervicis muscle. Venom-induced increases in [Ca(2+)](i) correlated with an increased cell death of cultured neurones as measured using propidium iodide (1 micro g/ml). Morphological analysis revealed cellular swelling and neurite loss consistent with necrosis. These data indicate that the effects of all three venoms are due in part to an increase in intracellular Ca(2+), possibly via the formation of pores in the cellular membrane which, under certain conditions, can lead to necrosis.     

Neuromuscular activity of the venoms of the Colombian coral snakes Micrurus dissoleucus and Micrurus mipartitus: An evolutionary perspective

The venoms of coral snakes (genus Micrurus) are known to induce a broad spectrum of pharmacological activities. While some studies have investigated their potential human effects, little is known about their mechanism of action in terms of the ecological diversity and evolutionary relationships among the group. In the current study we investigated the neuromuscular blockade of the venom of two sister species Micrurus mipartitus and Micrurus dissoleucus, which exhibit divergent ecological characteristics in Colombia, by using the chick biventer cervicis nerve-muscle preparation. We also undertook a phylogenetic analysis of these species and their congeners, in order to provide an evolutionary framework for the American coral snakes. The venom of M. mipartitus caused a concentration-dependant inhibition (3-10 μg/ml) of nerve-mediated twitches and significantly inhibited contractile responses to exogenous ACh (1 mM), but not KCl (40 mM), indicating a postsynaptic mechanism of action. The inhibition of indirect twitches at the lower venom dose (3 μg/ml) showed to be triphasic and the effect was further attenuated when PLA2 was inhibited. M. dissoleucus venom (10-50 μg/ml) failed to produce a complete blockade of nerve-mediated twitches within a 3 h time period and significantly inhibited contractile responses to exogenous ACh (1 mM) and KCl (40 mM), indicating both postsynaptic and myotoxic mechanisms of action. Myotoxic activity was confirmed by morphological studies of the envenomed tissues. Our results demonstrate a hitherto unsuspected diversity of pharmacological actions in closely related species which exhibit divergent ecological characteristics; these results have important implications for both the clinical management of Coral snake envenomings and the design of Micrurus antivenom.     

Isolation and pharmacological characterisation of papuantoxin-1, a postsynaptic neurotoxin from the venom of the Papuan black snake (Pseudechis papuanus)

The Papuan black snake (Pseudechis papuanus) is found throughout the southern coastal regions of Papua New Guinea and is thought to occur in the adjacent region of Iriyan Jaya. Neurotoxicity is a major symptom of envenomation by this species. This study describes the isolation of the first neurotoxin papuantoxin-1 from the venom of P. papuanus. Papuantoxin-1 (6738Da), which accounts for approximately 5% of the whole venom, was purified to homogeneity using successive steps of RP-HPLC. The toxin (0.3-1.0 microM) caused concentration dependent inhibition of indirect twitches (0.1 Hz, 0.2 ms and supramaximal V) and inhibited the responses to nicotinic agonists in the chick biventer cervicis nerve-muscle preparation, indicating a postsynaptic mode of action. However, papuantoxin-1 displayed no signs of myotoxicity. Papuantoxin-1 displayed pseudo-irreversible antagonism of cumulative concentration-response curves to carbachol at the skeletal muscle nicotinic receptors with an estimated pA2 value of 6.9+/-0.3. CSL black snake antivenom, which is raised against the venom of the Australian black snake Pseudechis australis, appears to be effective in reversing the effects of papuantoxin-1. Thus, black snake antivenom should be considered for the treatment of the neurotoxic effects following envenomation by the Papaun black snake.     

The interaction of some kynurenine pathway metabolites with 5-hydroxytryptophan and 5-hydroxytryptamine

The kynrenine pathway metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid have been tested against 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP)-induced head twitches in the mouse in a dose-range of 0.5–5.0 mg/kg. Kynurenine and 3-hydroxykynurenine were highly active. Low doses caused marked potentiation of the twitch response to both 5-HT and 5-HTP with increased toxicity of 5-HT. High doses caused antagonism of both responses. Xanthurenic acid was inactive over the same dose range. The effects of kynurenine could not be duplicated in the guinea-pig ileum. The relevance of these results to the involvement of kynurenine pathway metabolites in depressive illness is discussed.     

Pharmacological studies on the bungarotoxins: separation of the fractions and their neuromuscular activity

A commercial sample of Bungarus multicinctus venom was separated into its constituent fractions by column chromatography on CM-Sephadex C-50. The fractions were tested on the responses of the chick biventer cervicis preparation to nerve stimulation, and to added acetylcholine and carbachol.13 fractions were obtained: 1 was inactive, 4 exhibited weak postjunctional neuromuscular blocking activity, 3 had potent postjunctional blocking activity, and the remaining 5 fractions exhibited predominately prejunctional blocking activity. Use of higher concentrations of the prejunctional toxins revelead that 2 of these fractions also possessed some postjunctional blocking activity.Because small differences in separation procedures may result in differences in the elution pattern of the venom, and because some fractions may possess nonspecific actions only obvious at high concentrations, it is suggested that, when using venom components as experimental tools, the separation method is detalied and the fractions thoroughly tested.     

Effect of lithium on central metabolism of 5-hydroxytryptamine

The administration of lithium carbonate for 5 days to rats increased the synthesis rate of brain serotonin, without modifying the brain level of the amine. This increase was not due to a modification of the free tryptophan in the blood. The level of serotonin and 5 HIAA remained unchanged in seven areas of brain. These results are discussed in comparison with the results of the other authors on the same subject.Attachée de recherche INSERM.     

Comparison of the neurotoxic and myotoxic effects of Brazilian Bothrops venoms and their neutralization by commercial antivenom.

The venoms of some Bothrops species produce neuromuscular blockade in avian and mammalian nerve-muscle preparations in vitro. In this study, we compared the neuromuscular activities (myotoxicity and neurotoxicity) of venoms from several Brazilian species of Bothrops (B. jararaca, B. jararacussu, B. moojeni, B. erythromelas and B. neuwiedi) in chick isolated biventer cervicis muscle preparations and examined their neutralization by commercial antivenom. All of the venoms (50-200 microg/ml, n = 3 - 7 each) induced long-lasting, concentration-dependent muscle contracture and twitch-tension blockade, and also inhibited the muscle responses to acetylcholine and KCl. Preincubation of the venoms (200 microg/ml) with bothropic antivenom (0.2 ml) for 30 min at 37 degrees C prevented the twitch-tension blockade to different extents, with the protection varying from 0.5% (B. neuwiedi) to 88% (B. moojeni). Complete protection against the neuromuscular action of B. neuwiedi venom was observed only with a mixture of bothropic and crotalic antivenoms. The venoms caused either high (B. jararacussu, B. neuwiedi and B. moojeni) or low (B. jararaca and B. erythromelas) creatine kinase release. Morphologically, myonecrosis was greatest with B. jararacussu venom (98-100% of fibers damaged) and least with B. jararaca venom (74% damage). The extent of neutralization by bothropic antivenom was B. jararaca (93%)>B. erythromelas (65.8%)>B. moojeni (30.7%)>B. neuwiedi (20%)>B. jararacussu (no neutralization). Despite this variation in neutralization, enzyme-linked immunosorbent assays indicated similar immunoreactivities for the venoms, although immunoblots revealed quantitative variations in the bands detected. These results show that Bothrops venoms produce varying degrees of neuromuscular blockade in chick nerve-muscle preparations. The variable protection by antivenom against neuromuscular activity indicates that the components responsible for the neuromuscular action may differ among the venoms.     

Accumulation of basic drugs in 5-hydroxytryptamine storage organelles of rabbit blood platelets.

The subcellular distribution of basic substances such as mepacrine, chloroquine, chlorpromazine and imipramine was studied in rabbit blood platelets exposed to these compounds in vitro and to some in vivo. All the drugs showed a preferential concentration in the 5-hydroxytryptamine (5HT) storage organelles (5HT vesicles). Chloroquine and mepacrine accumulated more specifically in the organelles than did chlorpromazine and imipramine. After osmotic shock of the 5HT vesicles chlorpromazine sedimented mostly with the vesicular membranes, whereas the other compounds preferentially went into the supernatant. It is concluded that (a) fluorescent basic compounds such as mepacrine are rather specific markers for the 5HT storage organelles in live platelets and (b) drugs such as chlorpromazine and imipramine also have a considerable affinity for these organelles.     

Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam

This study examined the effects of various drug treatments (IP injections) proposed to modify central 5-hydroxytryptamine (5-HT) activity on a conditioned suppression of drinking behavior in water-deprived rats. The subjects were trained to drink their daily water requirement during a 10-min session. Intermittent tone periods of 7 s were then introduced, the last 5 s of which the drinking tube was electrified. The animals gradually suppressed tube contacts during the tone to a low constant level within 2 weeks of training. Diazepam increased punished responding dramatically. The 5-HT antagonists methysergide (1–18 mg/kg), cyproheptadine (1–18 mg/kg), metergoline (0,25–2.0 mg/kg) and cinanserin (10–100 mg/kg) failed to induce large, reliable increases in punished responding. When a low dose of diazepam was combined with 5-HT antagonists, only one treatment, methysergide at 3 mg/kg, potentiated the anticonflict activity of diazepam. Acute or chronic treatment with PCPA increased behavior suppressed by punishment, but this effect was weak, brief, and poorly related to the depletion of brain 5-HT. LSD (0.3–100 g/kg) administered 1,10, or 30 min before the test was ineffective in overcoming suppression by punishment. Mescaline (6–30 mg/kg) had no significant effect on punished responding. 5-HTP (18 mg/kg) decreased the number of shocks accepted, but not after pretreating with carbidopa. Pretreatment with carbidopa plus 5-HTP potentiated the anticonflict effect of diazepam. The 5-HT agonist mCPP (0.25–2.0 mg/kg) enhanced suppression due to punishment, but only in doses that interfered with unpunished responding. The 5-HT-releasing agent fenfluramine (0.25–1.0 mg/kg) did not affect this behavior. Amitriptyline pretreatment in a dose not affecting unpunished behavior (5.6 mg/kg) potentiated the diazepam-induced increase in punished responding. These results are difficult to reconcile with the proposal that suppression of behavior consequent to punishment is related to brain 5-HT activity.     

The effects of 5-hydroxytryptamine and some related compounds on the cat superior cervical ganglion in situ

Summary The effects of 5-hydroxytryptamine (5-HT) and related indole derivatives injected as i.a. bolus injections in a large dose range were studied in the cat superior cervical ganglion (SCG) by recording ganglionic and postganglionic electrical activity. 5-HT had two independent and opposite actions: a long-lasting inhibition of ganglionic transmission occurred already with extremely low doses and increased up to highest ones: both pre-and postsynaptic sites of action seem to be involved. In a medium and high dose range, the inhibitory effect was temporarily masked by a short-lasting stimulation and a depolarisation which was small when compared with that produced by nicotinic agents. The depolarization triggered a secondary hyperpolarization. The stimulant, but not the inhibitory action was very prone to tachyphylaxis.LSD, methysergide, psilocybin and N,N-dimethyltryptamine (DMT) possess only the inhibitory property of 5-HT. The two N,N-dimethylated derivatives bufotenine and DMT, as well as the -methylated 5-HT stimulated nicotinic receptors, bufotenine in addition to, and 5-hydroxy--methyltryptamine in the absence of typical 5-HT-like inhibitory and excitatory activity. Tryptamine had neither inhibitory nor excitatory 5-HT-like actions, it depolarized and blocked transmission by an unknown mechanism. 5-Hydroxy--methyltryptamine and -methyltryptamine seem to have a marked affinity for, but no intrinsic activity at excitatory 5-HT receptors; they blocked the excitatory effect of 5-HT.     

中药石菖蒲对脑内单胺类神经递质5-羟色胺水平的影响

目的:观察石菖蒲各提取部分对小鼠大脑内5-羟色胺(5-HT)含量的影响。方法:通过给小鼠灌服石菖蒲不同提取部分,用高效液相色谱-电化学检测法分别测定小鼠大脑内5-HT的含量,研究石菖蒲各提取部分对5-HT含量的影响。结果:小鼠灌服石菖蒲后大脑内5-HT的含量变化如下:石菖蒲挥发油组,石菖蒲水煎液及全方组5-HT的含量均比空白组显著升高(P<0.05,P<0.01,P<0.01)。结论:石菖蒲可显著增加小鼠大脑内5-羟色胺的含量,以此推测石菖蒲很可能通过上调脑内5-HT水平,促进血脑屏障的开放。     

Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; mediation of tachycardia by 5-HT1-like receptors

Summary The effects of 5-hydroxytryptamine (5-HT) on heart rate in anaesthetized cats were analysed both in intact animals and after spinal section plus vagotomy.The intact cat responded to 5-HT (3, 10 and 30 g·kg^–1, i.v.) with a brief, but intense, bradycardia and a longerlasting hypotension. Administration of MDL 72222, a selective antagonist of M-type 5-HT receptors, blocked bradycardia elicited by 5-HT without affecting that caused by stimulation of the vagus nerve.In spinal cats the same doses of 5-HT increased heart rate and blood pressure. These effects remained essentially unchanged after bilateral adrenalectomy, guanethidine, propranolol and burimamide, suggesting that 5-HT acted directly on the myocardium and blood vessels. The tachycardic responses to 5-HT in spinal cats were little affected by 0.5 mg·kg^–1 doses of MDL 72222 or of the 5-HT₂ receptor antagonists, ketanserin, ritanserin or cyproheptadine. In contrast, the non-selective 5-HT receptor antagonist, methysergide, which binds to both 5-HT₁ and 5-HT₂ recognition sites in rat brain membranes, potently antagonized the 5-HT-induced tachycardia in doses of 0.05 to 0.5 mg·kg^–1. However pizotifen and mianserin, two other 5-HT₂ antagonists which show poor affinity for 5-HT₁ recognition sites, were also effective against the tachycardic response to 5-HT in doses of 0.5–4.5 mg·kg^–1. The pressor responses to 5-HT in the spinal cat were markedly inhibited by all six 5-HT₂ antagonists at a dose of 0.5 mg·kg^–1.5-Carboxamido-tryptamine, which has a high and selective affinity for 5-HT₁ recognition sites, elicited marked tachycardia in doses of 0.1–10 g/kg^–1 in spinal cats treated with saline. These responses were not affected in animals treated with 4.5 mg·kg^–1 of ketanserin, which was able to shift the dose-response curve for 5-HT to the right. On the other hand, methysergide (0.5 mg·kg^–1) displaced the dose-response curves for both 5-carboxamidotryptamine and 5-HT to a similar extent.Unlike on the dog saphenous vein, methysergide showed no agonist effects on heart rate in the spinal cat.On the basis of the above results, we conclude that: (i) the reflexogenic bradycardic response elicited by 5-HT overshadows its direct tachycardic response on heart rate in the intact cat; (ii) M-type 5-HT receptors mediate the bradycardic response; (iii) the pressor response to 5-HT in the spinal cat involves 5-HT₂ receptors; (iv) tachycardia by 5-HT in the spinal cat is mediated mainly by 5-HT₁-like receptors, but an additional, though less important, non-5-HT₁ mechanism may also be involved; (v) the cardiac 5-HT₁ receptors are similar, but perhaps not identical, to those delineated in the dog saphenous vein or rat brain membrane preparations; and (vi) the tachycardic responses to 5-HT and, in particular the more selective, 5-carboxamidotryptamine may be conveniently utilized to characterize new chemical compounds designed for potential 5-HT₁ receptor antagonist activity.     

Investigations of cardiovascular 5-hydroxytryptamine receptor subtypes in the rat

Summary Peripheral 5-HT receptor-mediated responses were examined in pithed spontaneously hypertensive rats and normotensive wistar rats. Responses examined were: Pressor and depressor responses, tachycardia and inhibition of stimulation-evoked tachycardia. In pithed spontaneously hypertensive rats, 5-HT, but not the 5-HT₁-selective agonist 5-carboxamidotryptamine, produced pressor responses, and these were potently antagonised by the 5-HT₂-selective antagonists ketanserin and LY 53857. In pithed spontaneously hypertensive rats, the tachycardia to 5-HT was abolished by a combination of the 5-HT₂ receptor antagonist LY 53857 and propranolol, suggesting that the tachycardia is mediated by 5-HT₂ receptors and by release of noradrenaline. In pithed spontaneously hypertensive rats, 5-carboxamidotryptamine, 5-HT, and to a lesser extent the 5-HT₁ receptor agonist RU 24969, but not the 5-HT_1A receptor agonist 8-OH-DPAT, produced depressor responses which were antagonised by methysergide and metitepin, but which do not clearly fit with any of the 5-HT, ligand binding sites. In pithed normotensive wistar rat, 5-carboxamidotryptamine was approximately 100 times more potent than 5-HT and 8-OH-DPAT at inhibiting the cardio-acceleration produced by single pulse electrical stimulation and this inhibition was antagonised by metitepin, so that the response is mediated by 5-HT₁ receptors.     

Pharmacological studies on the bungarotoxins: an analysis of the site of action of nicotinic agonists

The possibility that nicotinin agonists may exert an indirect action by releasing endogenous acetylcholine from nerve terminals has been examined by the use of nerve-free cultured muscle, and by the use of the specifically prejunctionally active β-type bungarotoxins.In cultured muscle the depolarizations produced by acetylcholine and carbachol were not greatly affected by treatment of the cultures with β-type bungarotoxins for 60 min.In the chick biventer cervicis nerve-muscle preparations dose-response curves to acetylcholine, carbachol, dimethylphenylpiperazinium and nicotine were not affected even after abolition of responses to nerve stimulation by the β-types toxins.As the responses to nicotinic agonists were obtainable in nerve-free muscle and were unimpaired in the chick biventer after elimination of nerve function by β-type bungarotoxins, we conclude that such agonists exert a direct action on the postjunctional acetylcholine receptors.     

Ethanol potentiation of choline,acetylcholine, carbachol and phenyltrimethylammonium contractions in the chick biventer cervicis muscle

Pretreatment of chick biventer cervicis preparations with ethanol (290 mM) potentiated the EC₅₀ of choline, acetylcholine, carbachol and phenyltrimethylammonium 91%, 319%, 97% and 213%, respectively. Perhaps this interaction of ethanol and neurotransmitter could contribute to the effects on coordination and motor activity produced by ethanol in vivo.     

Further observations on the effect of repeated electroconvulsive shock on the behavioural resposes of rats produced by increases in the functional activity of brain 5-hydroxytryptamine and dopamine

Following repeated electroconvulsive shocks (ECS) (once daily for 10 days), rats display enhanced hyperactivity responses to tranylcypromine and l-tryptophan, a procedure which increases brain 5-hydroxytryptamine (5-HT) concentrations, or to the suggested 5-HT agonist quipazine. The enhanced responses last for about 6 days following the last shock. Repeated sub-convulsive shocks did not produce this behavioural enhancement.Administration of indomethacin (2 mg/kg) 25 min before the ECS did not prevent the enhanced 5-HT response suggesting that the enhanced response is not the result of the reported rise in prostaglandins F following ECS.Repeated ECS shortened the time to loss of righting following pentobarbital (50 mg/kg) but did not alter the total sleeping time.Repeated ECS enhances locomotor activity produced by methamphetamine. It also enhances circling produced by methamphetamine and apomorphine in unilateral nigrostriatal lesioned rats, suggesting an enhanced postsynaptic response.No evidence was found for ECS altering the response of striatal adenylate cyclase to dopamine nor for any alteration of striatal cyclic AMP concentration.These data taken with our previous study reinforce the suggestion that electroconvulsive therapy (ECT) produces increased responses to 5-hydroxytryptamine and dopamine receptor stimulation.