In vivo voltammetric study of cortical 5-HT after administration of 5-HTP or paroxetine to phenelzine-treated rats.
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5-Hydroxytryptophan↗
Biomedical subjects
J D Stephenson
Publications and source records attributed to J D Stephenson.
A putative non-cholinergic mechanism in urinary bladders of New but not Old World primates.
The effects of atropine on bladder contractions evoked by sacral ventral root stimulation were investigated in two species of New World monkey (marmoset and cebus) and in paraplegic man. The findings were then compared to those previously obtained for the cat and two species of Old World monkey (rhesus and baboon). The results show the marmoset and cebus to represent a transitional stage between the complete sensitivity of the bladders of Old World monkeys to atropine and the relative insensitivity of the cat bladder. The bladder response is shown to comprise two components, an atropine sensitive component which is slow in onset and an atropine resistant component which is easily fatigued. The experiments in paraplegic people confirm that the parasympathetic innervation of the bladder of man is, like that of Old World monkeys, exclusively cholinergic. A behavioural interpretation is tentatively offered to explain the two types of innervation.
Animals↗
Effects of antidepressant drug combinations on cortical 5-HT2 receptors and wet-dog shakes in rats.
Rats pretreated with the monoamine oxidase inhibitor, phenelzine 18 h (46.8 mg/kg) and 90 min (11.7 mg/kg) previously or only 90 min (46.8 mg/kg) previously developed a 5-HT dependent syndrome (including wet-dog shakes, WDS) when given the 5-HT uptake inhibitor, paroxetine (11.6 mg/kg). After 2 h, but only in rats pretreated with 2 injections of phenelzine, there was a gradual reduction in the number of cortical 5-HT2 receptors, determined in vitro with [3H]ketanserin, and this was temporally related to a reduction in the frequency of WDS. Both effects (down-regulation and WDS) were prevented by the 5-HT2 receptor antagonist, pirenperone. A second injection of paroxetine at 3 h evoked additional WDS in rats pretreated with 1 injection of phenelzine but not in rats pretreated with 2 injections, suggesting that spinal 5-HT2 receptors might also have been down-regulated at the same time. Similar results were obtained when rats were pretreated instead with the selective MAO A inhibitor, clorgyline or when given either citalopram or fenfluramine instead of paroxetine. 5-HTP also evoked WDS in phenelzine-treated rats and markedly increased brain 5-HT concentration but only slowly down-regulated 5-HT2 receptors; in carbidopa-treated animals, 5-HTP was without effect on receptor numbers despite production of frequent WDS. It thus appears that drugs which increase synaptic 5-HT (as indicated by production of WDS) by interference with the release or reuptake of 5-HT more readily down-regulate 5-HT2 receptors than 5-HTP which does not directly affect these mechanisms.
5-Hydroxytryptophan↗
Is waning of a 5-hydroxytryptamine (5-HT)-mediated syndrome due to 5-HT2 receptor down-regulation?
The 5-hydroxytryptamine (5-HT) uptake inhibitor, paroxetine (11.6 mg/kg i.p.), given to rats pretreated with the monoamine oxidase inhibitor, phenelzine, 18 h (46.8 mg/kg i.p.) and 90 min (11.7 mg/kg i.p.) before, evoked a 5-HT-dependent syndrome which included wet-dog shakes (WDS). The frequency of WDS declined over the ensuing 3 h, at which time cortical 5-HT2 receptors showed a significant (30%) decrease in number. A second injection of paroxetine given at this time did not evoke a significant increase in the number of WDS, suggesting that spinal 5HT2 receptors might also have been down-regulated at the same time.
Animals↗
Effects of some atypical antidepressants on beta-adrenoceptor binding and adenylate cyclase activity in the rat forebrain.
The effects of daily administration to rats of desipramine, talsupram, tomoxetine, maprotiline, nomifensine, mianserin and citalopram (each 10 mg kg-1 day-1) for 4 weeks on [3H]dihydroalprenolol ([3H]DHA) binding in the cerebral cortex and on the noradrenaline-sensitive adenylate cyclase in the limbic forebrain were determined. Of these compounds, desipramine was alone in reducing [3H]DHA binding and in attenuating the cAMP response. Two selective noradrenaline uptake inhibitors, talsupram and tomoxetine each reduced the cAMP response but without affecting [3H]DHA binding. The other drugs lacked effect on both measures indicating (except for citalopram) that reduction in sensitivity of beta-adrenoceptors and of the noradrenaline-sensitive cAMP response might not be a simple consequence of noradrenaline uptake inhibition. The lack of effect of citalopram on the sensitivity of the beta-adrenoceptor system suggests that antidepressants with selective 5-HT uptake inhibitory properties owe their antidepressant activity to other mechanisms.
Adenylyl Cyclases↗
Effects of desipramine on cardiovascular responses of rats to stimulation of the baroreceptor reflex and of central adrenoceptors.
Phenylephrine (0.4-2.0 micrograms 300 g-1), injected intravenously, evoked similar dose-dependent increases in blood pressure in untreated rats and in rats treated with desipramine (10 mg kg-1 day-1 for 4 weeks). The (dose-dependent) reflex fall in heart rate to the blood pressure responses were smaller in the rats treated with desipramine. Treatment with desipramine did not affect the bradycardia evoked by intrahypothalamic injection of phenylephrine (10 micrograms). After treatment with desipramine, the hypotension evoked by intrahypothalamic injection of isoprenaline (10 micrograms) was enhanced whereas the evoked tachycardia was diminished.
Adenylyl Cyclases↗
Bladder electromyograms and function in monkeys after atropine.
Voiding induced in conscious monkeys by infusion of sterile saline into the bladder via a chronically implanted bladder catheter was stable over many months. Artefact-free recordings of electrical activity were obtained from the bladder neck and dome of these animals during bladder filling and voiding. Characteristic voiding electromyograms were recorded from both sites but were seen first in the record from the neck. Small doses of methyl-atropine abolished both voiding and the electromyograms; evoked responses to sacral ventral root stimulation were similarly prevented. Therefore the bladders of both man and monkey are very sensitive to atropine, unlike the bladders of most other animals.
Anesthesia↗
Effect of desipramine, phenoxybenzamine and yohimbine on beta-adrenoceptors and cyclic AMP production in the rat brain.
In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg-1 day-1), which is a more potent inhibitor of alpha 1 than alpha 2-adrenoceptors. The only treatment which significantly decreased the specific binding of the beta-adrenoceptor antagonist, [3H]dihydroalprenolol was the combination of desipramine with yohimbine. Desipramine alone and desipramine with yohimbine also significantly reduced the formation of cyclic AMP in response to incubation with noradrenaline, the response to the drug combination being accounted for by addition of the individual effects of the drugs. The results showed that decreases in the activity of noradrenaline-dependent adenylate cyclase could become apparent before decreases in beta-adrenoceptor numbers. Whether these rapid changes in noradrenaline-dependent adenylate cyclase or in numbers of beta-adrenoceptors which are produced by combination of desipramine with an alpha 2-adrenoceptor antagonist, are of therapeutic value remains to be elucidated.
Adenylyl Cyclases↗
The effects of parasympathetic blocking agents on bladder electromyograms and function in conscious and anaesthetized cats.
Voiding induced in conscious cats by infusion of sterile saline into the bladder via a chronically implanted bladder catheter was stable over many months. Artefact-free recordings of electrical activity obtained from the bladder neck and dome of these preparations during bladder filling and voiding showed characteristic voiding electromyograms but did not permit a functional differentiation. Both voiding and the associated electromyogram were abolished by the ganglion blocking agent, pentolinium. Hyoscine or methyl atropine did not affect the electromyogram but impaired the ability of cats to empty their bladders completely. In anaesthetized cats, ganglion blocking agents prevented a rise in bladder pressure during sacral ventral root stimulation but a hyoscine-sensitive bladder contraction was seen following the period of stimulation. Further stimulation during this post-stimulus rise in intravesical pressure revealed a hyoscine-sensitive stimulus-bound relaxation. Sacral ventral root stimulation relaxed the bladder neck/proximal urethra particularly in the presence of sympathetic tone.
Anesthesia↗
Susceptibility of Neisseria meningitidis and Neisseria gonorrhoeae isolates to N-formimidoyl thienamycin.
A diverse collection of 123 meningococcal and 126 gonococcal isolates was tested for susceptibility to N-formimidoyl thienamycin (N-F-thienamycin; MK0787) and to penicillin G (PEN). All of the meningococci were susceptible to both of these, as well as to rifampin. Among gonococci, beta-lactamase-producing strains, which were resistant to PEN, were susceptible to N-F-thienamycin. Among non-beta-lactamase-producing strains, the minimal inhibitory concentrations of N-F-thienamycin and PEN were less than or equal to 1.28 micrograms/ml. Of these, the strains with PEN minimal inhibitory concentrations toward the higher end of the range were likely to be more susceptible to N-F-thienamycin, whereas the strains that were highly susceptible to PEN were likely to have higher minimal inhibitory concentrations of N-F-thienamycin.
Anti-Bacterial Agents↗
Behavioral and electrocortical effects of beta-endorphin after intracerebral infusion in rats.
In rats with cannulae chronically implanted into specific areas of the brain, the effects of beta-endorphin were studied on behavior and electrocortical activity. It has been shown that analgesia and catatonia were evoked after infusing beta-endorphin into the III cerebral ventricle or into the hypothalamus. On the contrary, beta-endorphin microinjected into the caudate nucleus or into the substantia nigra produced an intense pattern of stereotyped movements, occasional contralateral circling, contralateral myoclonic jerks and asymmetric posture. Stereotyped gnawing, grooming and "wet-dog" syndrome preceded catatonia after intrahypothalamic administration of beta-endorphin. Bilateral (III ventricle) or ipsilateral (hypothalamus, caudate nucleus and substantia nigra) high voltage electrocortical spikes and other ECoG pathological changes accompanied by motor disorders (stereotypies, myoclonic jerks) or without any overt behavioral change were constantly observed. Behavioral and electrocortical changes evoked by beta-endorphin were long-lasting and rapidly reversed by the specific opiate antagonist, naloxone.
Animals↗
Stereotyped behaviour and electrocortical changes after intracerebral microinfusion of dopamine and apomorphine in fowls.
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Animals↗
Central effects of histamine and H1 and H2 receptors agonists and antagonists after intraventricular infusion in fowls.
In adult fowls (Gallus deomesticus) the effects of histamine H2 and H2 histamine receptors angonists and antagonists infused into the III cerebral ventricle were studied on behaviour, electrocortical activity and body temperature. Histamine produced biphasic effects, i.e. an initial period of electrocortical synchronization was followed by a longer-lasting behavioural stimulation, electrocortical desynchronization and shivering. Body temperature was increased in a dose-dependent manner. Dimaprit, an agonist at H2 receptors, produced behavioural and electrocortical sleep and decreased body temperature whereas, 2-(2-thiazolyl-)-ethyl-amine, an agonist at H1 receptors, behavioural stimulation, electrocortical desynchronization, vocalization and hyperthermia. Cimetidine, an antagonist at H2 receptors, produced intense behavioural stimulation and electrocortical desynchronization accompanied by vocalization, tachypnoea, occasional escape responses and stereotypies. Body temperature was increased. Mepyramine, an antagonist at H1 receptors, produced behavioural and electrocortical sleep and prevented behavioural excitation elicited by subsequent infusion of histamine and hyperthermia evoked by 2-(2-thiazolyl -ethylamine. Haloperidol, a neuroleptic drug, sharing with mepyramine membrane stabilizing properties, was unable to antagonize histamine-induced behavioural excitation. In conclusion, present experiments provide pharmacological evidence for the existence of H1 and H2 histamine receptors in avian brain and suggest an involvement of histamine H1 and H2 receptors in the control of arousal-sleep and thermoregulatory mechanisms.
Animals↗
Some effects of imipramine on micturition and their relevance to its anti-enuretic activity.
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Animals↗
Dopaminergic mechanisms and stereotyped behaviour in birds.
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Amphetamine↗
Physiological and pharmacological basis for the chemotherapy of enuresis.
Enuresis is a disorder of micturition occuring in the absence of an organic urinary tract lesion. To understand its possible causation, the mechanisms controlling micturition are described together with the possible sites of action of various anti-enuretic agents, particularly imipramine. It is concluded that further research into the central control of micturition is required before the precise actions of centrally-acting anti-enuretic agents can be elucidated. Knowledge of these may give insight into the nature of the defect causing enuresis.
Adolescent↗
Effects of noradrenaline and carbachol on temperature regulation of cold-stressed and cold-acclimated rats.
1 Noradrenaline (20 micrograms) and carbachol (1 microgram) injected into the anterior hypothalamus of rats at an ambient temperature of 23 degrees C evoked significant falls in core temperature and increases in tail temperature. 2 When rats were cold-stressed (4 degrees C for 90 min) or cold-acclimated (4 degrees C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature. 3 Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non-esterified fatty acid (NEFA) concentrations in control, acutely cold-stressed and cold-acclimated rats. 4 Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4 degrees C for 1 to 28 days, glucose oxidation rate of both cold-stressed and cold-acclimated rats was significantly greater than in rats at 23 degrees C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.
Acclimatization↗
Effects of noradrenaline and carbachol on temperature regulation of rats.
1 Noradrenaline (0.2 to 20 micrograms) and carbachol (0.1 to 1 microgram) injected into the preoptic/anterior hypothalamic area, evoked dose-dependent falls in core temperature at all sites tested, followed in most experiments by delayed increases that were not dose-related. Muscarine (0.1 to 10 microgram) produced effects similar to those evoked by carbachol. 2 These falls in core temperature were associated with increases in tail temperature, locomotor activity and CO2 elimination (a measure of metabolic rate). 3 The temperature responses to noradrenaline (10 microgram) and to carbachol (1 microgram) were antagonized by intrahypothalamic injections of phentolamine (10 microgram) and atropine (1 microgram), respectively. 4 Analysis of the temperature responses and their respective latencies indicates that carbachol-induced hypothermia was mediated by cholinoceptors in the anterior hypothalamus, whereas hypothermia after noradrenaline was mediated by adrenoceptors throughout the preoptic/anterior hypothalamic area. 5 Vasodilatation of the tail blood vessels contributed significantly to the hypothermia evoked by carbachol, and to that evoked by injections of noradrenaline into the anterior hypothalamus. 6 Hypothermia induced by noradrenaline injection into the preoptic area, was mediated by effector mechanisms additional to non-evaporative heat loss.
Animals↗