Interaction of diphenhydramine with cholinesterase inhibitors in mice

Physostigmine (1.5 mg/kg, s.c.) and neostigmine (1.0 mg/kg, s.c.) injection into male mice produced signs of toxicosis characteristic of cholinesterase inhibition and evoked death in 95 and 94% of the animals respectively. Diphenhydramine injections (5-30 mg/kg, s.c.) 15 min before physostigmine or neostigmine significantly increased the latency period to onset of death and the percentage of survivors. Diphenhydramine injection (20 mg/kg, s.c.) between -30 and +2 min (but not at +5 and +10 min) relative to physostigmine prevented lethality in 100% of the animals. The data indicated that diphenhydramine which possesses anticholinergic effects protected mice against physostigmine- and neostigmine-induced toxicosis.     

Medetomidine protection against diazinon-induced toxicosis in mice

The protective effect of the α2-agonist medetomidine against the organophosphorus insecticide diazinon-induced toxicosis was examined in male mice. Oral dosing of diazinon at 75 and 100 mg/kg produced signs of toxicosis in mice characteristic of cholinergic over-stimulation, and the percentages of deaths were 90 and 100%, respectively. Subcutaneous (s.c.) injection of medetomidine at 0.05, 0.1 and 0.3 mg/kg, 15 min before diazinon (75 mg/kg, orally) significantly and dose-dependently decreased the incidence of toxic manifestations, delayed the onset of tremors and death, and increased the 24 h survival rates to 70, 80 and 100%, respectively. Similarly medetomidine pretreatments (0.1 and 0.3 mg/kg s.c) significantly protected the mice from the toxicity of a high dose (100 mg/kg, orally) of diazinon, and increased the 24 h survival rates to 38 and 50%, respectively. The α2-antagonist atipamezole significantly abolished the protective effect of medetomidine. When atropine sulfate (6 mg/kg s.c.) was combined with medetomidine (0.3 mg/kg s.c.) the degree of protection against diazinon toxicosis was more than that produced by either drug alone. The data suggest that medetomidine protected mice against diazinon-induced toxicosis, and a combination of medetomidine and atropine produced an even greater degree of protection.     

Influences of dopamine receptors on chewing behaviour in rats.

1. Intraperitoneal (i.p.) injection of different doses of pilocarpine induced purposeless chewing in rats. Physostigmine (i.p.), but not neostigmine (i.p.) also induced chewing behaviour. 2. Subcutaneous (s.c.) pretreatment of animals with the D-1 receptor blocker SCH 23390 decreased the number of chews induced by pilocarpine. 3. The D-2 dopamine antagonist sulpiride (i.p.) and anticholinergic atropine (i.p.) pretreatment also decreased the frequency of chews induced by the drug. 4. The response induced by pilocarpine (1 mg/kg i.p.) also was dose-dependently decreased in animals pretreated with apomorphine (0.25-1 mg/kg s.c.). 5. Administration of low doses of apomorphine (s.c.) also induced chewing, which was decreased with increasing the doses of the drug. 6. Chewing-induced by apomorphine was decreased by sulpiride or atropine and increased by SCH 23390 pretreatment. 7. Single administration of D-2 dopamine agonist bromocriptine also showed a slight but significant purposeless chewing, which was decreased by sulpiride pretreatment. 8. Single administration of D-2 agonist quinpirole, D-1 agonist SKF 38393 or D-1 antagonist SCH 23390, but not sulpiride caused a slight chewing. 9. It may be concluded that D-1 or D-2 activation exert opposite influences on chewing behaviour in rats, although to prove this effect more elucidation is needed.     

Morphine inhibits dopaminergic and cholinergic induced ejaculation in rats

1. Subcutaneous injection (s.c.) of apomorphine (0.1–0.5 mg/kg) and intraperitoneal administration (i.p.) of quinpirole (0.01–0.25 mg/kg), physostigmine (0.05–0.2 mg/kg) and philocarpine (0.75–3 mg/kg, i.p.) but not neostigmine (0.1–1 mg/kg) induced ejaculation in rats.2. The responses of drugs were reduced by morphine (1–6 mg/kg, s.c.) pretreatment.3. The inhibitory effect of morphine was reversed by naloxone (1.5 mg/kg, s.c.).4. Naloxone (0.75–3 mg/kg, s.c.) alone induced slight but significant ejaculation.5. Ejaculatory responses induced by apomorphine and quinpirole but not those by physostigmine and pilocarpine were reduced by sulpiride (100 mg/kg, i.p.) pretreatment.6. Domperidone (1–30 mg/kg, i.p.) did not change the response induced by apomorphine.7. Pretreatment of animals with the cholinergic antagonist atropine (10 mg/kg, i.p.) decreased the frequency of ejaculation induced by apomorphine, quinpirole, physostigmine or pilocarpine.8. It may be concluded that D-2 activation induces ejaculation through influence on cholinergic mechanisms and morphine inhibits the ejaculation induced by activation of both cholinergic and dopaminergic systems via opiate receptor sites.     

Effect of diphenhydramine on organophosphorus insecticide toxicity in mice

Male mice were treated orally with the organophosphorus insecticides fenamiphos and dichlorvos at 10 and 150 mg/kg, respectively. The insecticides produced signs of toxicosis characteristic of cholinesterase inhibition, and induced death in all treated mice. Pretreatment of mice with diphenhydramine HCl (20 and 30 mg/kg, subcutaneously) 15 min before either insecticide significantly (P less than 0.05) reduced the incidence of toxic manifestations (excessive salivation, Straub tail, and whole body tremor), delayed the onset of death, and increased the percentage of survivors. Doses of diphenhydramine less than 20 mg/kg were not so effective. The data indicated a protective property of diphenhydramine against organophosphorus insecticide-induced toxicosis.     

In-vivo modulation of central 5-hydroxytryptamine (5-HT1A) receptor-mediated responses by the cholinergic system

The aim of the present study was to investigate a putative modulation of rat 5-HT system by the muscarinic receptor antagonist atropine using in-vivo electrophysiological and behavioural techniques. In the dorsal raphe nucleus, administration of atropine (1 mg/kg i.v.) prevented the suppressant effect of the selective serotonin reuptake inhibitor paroxetine (0.5 mg/kg i.v.) on the spontaneous firing activity of 5-HT neurons, suggesting that atropine could induce an attenuation of somatodendritic 5-HT1A autoreceptors responsiveness. The 5-HT1A receptor agonist 8-OH-DPAT decreased both immobility in the forced swim test and the body core temperature. Pre-treatment with atropine (5 and 10 mg/kg i.p.) enhanced antidepressant-like effect of 8-OH-DPAT (1 mg/kg s.c.) and reduced 8-OH-DPAT (0.1 mg/kg s.c.)-induced hypothermia. In conclusion, the present study reports a functional role of muscarinic receptors in the modulation of pre- and post-synaptic 5-HT1A receptors mediated responses.     

Influence of different histamine receptor agonists and antagonists on apomorphine-induced licking behavior in rat

The effects of different histamine receptor agonists and antagonists on apomorphine-induced licking behavior in rats were investigated. Subcutaneous (s.c.) injection of various doses of apomorphine (0. 125-1.25 mg/kg) induced licking. The licking response was counted by direct observation and recorded for a 75-min period. Intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the histamine H(1) or H(2) receptor agonist, HTMT (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide) (50 and 100 microg per rat), or dimaprit (10 and 15 mg/kg, i.p.), respectively, potentiated apomorphine-induced licking, while the histamine H(3) receptor agonist, imetit (5 and 10 mg/kg, i.p.), reduced the licking response induced by apomorphine. Pretreatment with various histamine receptor antagonists, dexchlorpheniramine (30 and 40 mg/kg, i.p.), diphenhydramine (20, 30 and 40 mg/kg, i.p.), famotidine (30 and 40 mg/kg, s.c.) and ranitidine (20, 30 and 40 mg/kg), reduced apomorphine-induced licking, while thioperamide (5 and 10 mg/kg, i.p.) potentiated the apomorphine effect. The effects of HTMT and dimaprit were blocked by dexchlorpheniramine (20 mg/kg, i.p.) and famotidine (20 mg/kg, s.c.), respectively. The inhibitory effect elicited by imetit on apomorphine-induced licking behavior was also abolished in animals treated with thioperamide (2.5 mg/kg, i.p.). The results suggest that histaminergic mechanisms may be involved in the modulation of apomorphine-induced licking behavior.     

The treatment of delayed polyneuropathy induced by diisopropylfluorophosphate in hens

This study was undertaken to examine the influence of atropine, oximes and benzodiazepine on organophosphate-induced delayed polyneuropathy (OPIDP) in hens, which were poisoned with diisopropylfluorophosphate (DFP). The birds were treated with a standard neuropathic dose of DFP (1.1 mg/kg, s.c.), which produced typical signs of OPIDP. The development of OPIDP was observed within the followings 22 days. All drugs were given subcutaneously (s.c.), intramuscularly (i.m.) or intraperitoneally (i.p.), 20 min before the poison. The results obtained have shown that atropine (20 mg/kg, i.p.) only in combination with oxime TMB-4 (15 mg/kg, i.m.) produced significant improvement of OPIDP symptoms in comparison with positive control. Clinical signs and symptoms of OPIDP in the group which was treated with atropine (20 mg/kg, i.p.), TMB-4 (15 mg/kg, i.m.) and midazolam (2.5 mg/kg, i.m.) were more improved than that in the presence of a combination of atropine and TMB-4. The results of these experiments have shown that it is possible to prevent the development of DFP-induced OPIDP in hens by treatment with atropine and TMB-4 or atropine, TMB-4 and midazolam when given before DFP.     

Influence of some dopaminoceptor agents on nitrazepam-induced sleep in the domestic fowl (Gallus domesticus) and rats

The influence of apomorphine, levodopa and haloperidol was studied on nitrazepam sleep using young chicks and rats. In addition, the influence of dopamine and ADTN was studied in young chicks. Nitrazepam dose-dependently (0.4-51.2 mg/kg, i.p.) induced behavioural sleep in chicks. However, higher doses of nitrazepam (12.8-51.2 mg/kg, i.p.) were required to induce behavioural sleep in rats. Dopamine (12.5-100 mg/kg, i.p.) and ADTN (2.5-80 mg/kg, i.p.) delayed the onset but prolonged nitrazepam sleep in chicks: these effects were statistically significant. Levodopa (12.5-100 mg/kg, s.c.) and apomorphine (0.2-0.8 mg/kg, s.c.) profoundly delayed the onset and shortened the duration of nitrazepam sleep in both chicks and rats. Noradrenaline (20-80 mg/kg, i.p.) shortened the onset and prolonged nitrazepam sleep in chicks. Pimozide (1-8 mg/kg, i.p.) potentiated nitrazepam sleep and antagonized the effects of dopamine, levodopa and ADTN on nitrazepam sleep in chicks. Similarly, haloperidol (0.5-1.0 mg/kg, i.p.) potentiated nitrazepam sleep and antagonized the effects of levodopa and apomorphine on nitrazepam sleep in rats. The EEG synchronization and decreased EMG induced by nitrazepam (1.6 mg/kg, i.p., and 12.8 mg/kg, i.p., for chicks and rats, respectively) were antagonized by levodopa (12.5 mg/kg, s.c.). The behavioural and electroencephalographical results suggest that enhancement of dopaminergic neurotransmission may be involved in the mechanisms of wakefulness in both chicks and rats.     

Studies on the role of central catecholaminergic mechanisms in the antidotal effect of the oxime HI 6 in soman poisoned mice

The effects of atropine and the oxime HI 6 on running performance, brain and plasma cholinesterase activity and brain catecholamines were investigated in mice intoxicated with sublethal doses of soman (100 g/kg s.c.). The running time on a rotating mash wire drum (total running time 60 min) after injection of soman was reduced to 17.2 min. Treatment with atropine (10 mg/kg i.p.) or HI 6 (55 mg/kg i.p.) improved the running peformance to 48.2 and 44.8 min, respectively. Cholinesterase activity was decreased in soman poisoned mice to 47.3% in plasma and 43.5% in brain. Therapy with the oxime HI 6 resulted in a reactivation of soman-inhibited peripheral cholinesterase to 76.6%, but failed to reactivate central cholinesterase. Dopamine levels in mice brain were elevated in soman poisoning by 23.2%, whereas noradrenaline levels remained unchanged. The increase in brain dopamine levels was antagonized by atropine as well as by HI 6. The results of this study lead to the speculation that central dopaminergic mechanisms may be involved in soman toxicity as well as in the antidotal action of atropine and the mainly peripherally acting oxime HI 6.     

The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--2. Caesium.

Rats and mice were given either CsCl (3 mmol/kg, s.c.) or saline (as control), twice daily for 3 days. The administration of tranylcypromine (TCP) (15 mg/kg, i.p.) to rats pretreated with CsCl produced the 5-HT behavioural syndrome. Pretreatment with CsCl also enhanced the syndrome induced by p-chloroamphetamine (3 mg/kg, i.p.) or by TCP (15 mg/kg, i.p.) plus L-tryptophan (50 mg/kg, i.p.). p-Chlorophenylalanine (300 mg/kg, i.p., daily on 2 consecutive days) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by CsCl and TCP in rats. Pretreatment of rats with CsCl potentiated the 5-HT syndrome, elicited by the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.). Pretreatment with CsCl potentiated the 5-HT2-mediated head-twitches in the mouse but had no effects on hypothermia in the mouse induced by 8-OH-DPAT (0.5 mg/kg, s.c.). The rate of synthesis of 5-HT in the whole brain (excluding cerebellum) was enhanced by pretreatment with CsCl. The enhancement of 5-HT neuronal function by caesium may be related to its ability to block K(+)-channels in neuronal membranes.     

Neuronal mechanisms involved in drug-induced jumping behavior in mice

Previously we have found that lithium chloride (250 mg/kg i.p.) plus haloperidol (4 mg/kg i.p.), or apomorphine (0.25 mg/kg i.p.) plus thyrotropin releasing hormone (TRH, 20 mg/kg i.p.), elicited a jumping behavior which involves dopaminergic and cholinergic inhibition, and noradrenergic activation. Pretreatment with antiserotonergic agents such as methysergide (5 and 10 mg/kg i.p.) and cyproheptadine (5 mg/kg i.p.) enhanced the jumping behavior induced by these drugs. 5-Methoxy-N,N-dimethyltryptamine (5-MDMT, 5 mg/kg i.p.), a serotonergic receptor agonist, inhibited the jumping behavior. Muscimol, a GABA receptor agonist, at 2 mg/kg, potentiated jumping. GABA receptor antagonists such as bicuculline (4 mg/kg i.p.) and picrotoxin (0.2 and 1 mg/kg i.p.) depressed jumping. An antihistamine agent, diphenhydramine (5 mg/kg i.p.), also potentiated the jumping behavior. Furthermore methysergide (10 mg/kg i.p.), but not muscimol (2 mg/kg i.p.) elicited jumping behavior when combined with clonidine (0.5 mg/kg i.p.), TRH (20 mg/kg i.p.), haloperidol (4 mg/kg i.p.) or atropine (5 mg/kg i.p.). These results suggest that in addition to dopaminergic, cholinergic and noradrenergic mechanisms, serotonergic inhibition may be directly contributing to the initiation of jumping behavior, whereas GABAergic activation appears to be a modulating factor in this behavior.     

Induction of purposeless chewing behaviour in rats by 5-HT agonist drugs

The 5-HT agonist m-chlorophenylpiperazine (m-CPP; 1-16 mg/kg i.p. or s.c.), trifluoromethylphenylpiperazine (TFMPP; 2-16 mg/kg i.p.) and quipazine (2.5-20 mg/kg i.p.) increased purposeless chewing behaviour in rats. However, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.025-4 mg/kg s.c.) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 0.25-8 mg/kg s.c.) were without effect on chewing behaviour. Chewing behaviour induced by m-CPP (6 mg/kg s.c.) was antagonised by pretreatment with the 5-HT antagonists methiothepin and mianserin, but not by ketanserin or spiperone, or ICS 205-930. m-CPP (6 mg/kg s.c.)-induced chewing behaviour was also antagonised by pretreatment with (-)-propranolol (20 mg/kg). Pretreatment with the anticholinergic drugs benzhexol (2.5 mg/kg), and scopolamine (1 mg/kg) antagonised m-CPP (6 mg/kg s.c.)-induced chewing behaviour, but methylscopolamine (1 mg/kg) had no effect. These data support the role of 5-HT receptors in the mediation of purposeless chewing behaviour and suggest an interaction between brain 5-HT and acetylcholine systems.     

The effect of anti-Parkinsonian drugs on haloperidol-induced inhibition of the conditioned-avoidance response in rats

Haloperidol (200 μg/kg s.c.) inhibited the conditioned-avoidance response (CAR) in rats. Amantadine HC1 (12.5–50 mg/kg i.p.) produced a dose-dependent reduction in this inhibition. The reduction produced by apomorphine (10mg/kg i.p.) was more transient, and that produced by l-DOPA (200 mg/kg i.p.) was less marked than that produced by amantadine. Benzhexol (10 mg/kg i.p.), atropine (10 mg/kg i.p.) and BRL 1288 (10 mg/kg i.p.) produced no significant effect. The role of central dopamine mechanisms in these responses and the possible use of this procedure in screening anti-Parkinsonian drugs is discussed.     

Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.

In experiments in which mice were placed with their forepaws over a 4 cm high horizontal bar, delta-9-tetrahydrocannabinol (THC; 10 mg/kg i.p.) delayed descent from the bar. This effect on descent latency was markedly enhanced by physostigmine (0.05 or 0.25 mg/kg s.c.) and oxotremorine (0.04 or 0.08 mg/kg s.c.), administered immediately before THC. These interactions were attenuated by atropine (2.0 mg/kg s.c.) and (-)-scopolamine (1.9 mg/kg s.c.) but not by atropine methyl nitrate (2.11 mg/kg s.c.), which does not readily cross the blood-brain barrier. However, atropine methyl nitrate did prevent salivation induced by oxotremorine in the presence of THC. No synergism was detected between THC and neostigmine (0.047 mg/kg s.c.). Atropine and (-)-scopolamine also decreased the ability of chlordiazepoxide (10 mg/kg s.c.) to enhance the effect of THC on descent latency. The interaction was not antagonized by atropine methyl nitrate or mecamylamine (1.17 or 2.34 mg/kg s.c.). These results point to an involvement of central acetylcholine-releasing pathways in the cataleptic response of mice to THC.     

Endotoxin stimulates fecal pellet output in rats through a neural mechanism

The effects of endotoxin on fecal pellet output and the neural mechanisms involved in this response were investigated in conscious rats. E. coli endotoxin (40 micro g/kg i.p.) significantly increased fecal excretion for 3 h after the injection. Water content in feces was not modified by endotoxin. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats prevented the stimulatory effect of endotoxin and so did abdominal vagotomy. Adrenoceptor blockade with phentolamine (5 mg/kg i.p.) + propranolol (3 mg/kg i.p.) did not modify pellet output in endotoxin-treated rats while muscarinic receptor blockade with atropine (1 mg/kg i.p.) abolished the stimulatory effect of endotoxin. Finally, the increase in pellet output induced by endotoxin was prevented in animals receiving the substance P receptor antagonist D-Pro2, D-Trp7,9-substance P (2 mg/kg i.p.) or the NO-synthase inhibitor L-NAME (10 mg/kg i.p.). None of the above treatments modified pellet output in saline-treated rats.These observations indicate that endotoxin increases fecal pellet output through a nervous reflex in which capsaicin-sensitive afferent neurons and the release of excitatory (acetylcholine and substance P) and inhibitory (NO) neurotransmitters in the colonic wall are involved.     

Increase of plasma renin activity after subcutaneous application of compound 48/80 in the rat

Subcutaneous (s.c.) administration of compound 48/80 (3.0 mg/kg) to conscious rats produced a time-dependent long-lasting increase of plasma renin activity (PRA). A dose-related increase of the hematocrit was also observed after injection of compound 48/80. The onset of the hematocrit increase preceded that of PRA increase. Pretreatment with a dose of more than 20 mg/kg of histamine H1-receptor antagonists such as tripelennamine or diphenhydramine prior to the injection of compound 48/80 (3.0 mg/kg s.c.) attenuated or abolished the effects of compound 48/80 on PRA, hematocrit and plasma extravasation. Pretreatment with cimetidine (histamine H2-receptor antagonist, 40 mg/kg i.p.) had no effect on these plasma variables. The increase of PRA caused by s.c. administration of compound 48/80 was not affected by the pretreatment with propranolol (beta-adrenoceptor antagonist, 10 mg/kg i.p.), which completely inhibited the isoproterenol (0.5 mg/kg s.c.)-induced PRA increase. Administration of compound 48/80 did not induce a significant PRA increase in the nephrectomized rats although the increase of hematocrit following s.c. administration of compound 48/80 persisted despite the absence of kidneys. S.c. administration of compound 48/80 (3.0 mg/kg) led to a significant decrease of histamine content at the site of injection and to a significant increase in plasma histamine concentration without affecting arterial blood pressure. The present data suggest that s.c. administration of compound 48/80 stimulates the release of histamine from cutaneous mast cells, which cause an increase in vascular permeability to plasma protein via the stimulation of histamine H1-receptors, then leads to hypovolemia. The resulting hypovolemia may directly stimulate the juxtraglomerular cells of the kidney to release renin.     

The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--3. Quinine.

It has been shown that caesium, which shares properties with quinine as a K(+)-channel blocker, enhanced 5-HT-mediated behaviour in both rats and mice. It was therefore of interest to investigate the effects of quinine on 5-HT-mediated behaviour in the rat and mouse. Quinine, dose-dependently (ED50 = 5 mg/kg), produced the 5-HT behavioural syndrome in rats pre-treated with tranylcypromine (TCP) (15 mg/kg, i.p.). p-Chlorophenylalanine (i.p., 300 mg/kg x2) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by quinine (72 mg/kg, i.p.) plus TCP. The administration of quinine (72 mg/kg, i.p.) enhanced the 5-HT syndrome elicited by p-chloramphetamine (4 mg/kg, i.p.) and the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, i.p.), DOI (8 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.) in rats. Pretreatment with quinine also potentiated the 5-HT2-mediated head-twitch in the mouse but had no effect on the hypothermia in the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). Quinine also enhanced the rate of synthesis of 5-HT in the brain of the rat. On the basis of these findings, together with those in the preceding two papers, it is suggested that the effects of rubidium, caesium and quinine, to enhance differentially various aspects of 5-HT function are mediated by actions on 5-HT-modulated K(+)-channels. This conclusion is also discussed in relation to the actions of lithium and electroconvulsive shock on 5-HT function in brain and the treatment of manic-depressive disease.     

Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact actin cytoskeleton

The effects of endotoxin on gastric emptying of a solid nutrient meal and the neural mechanisms involved in such a response were investigated in conscious rats. The intraperitoneal (i.p.) administration of E. coli endotoxin (40 microg/kg) significantly reduced the 4-h rate of gastric emptying of a standard solid nutrient meal. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats did not modify the rate of gastric emptying in control animals but prevented the delay in gastric transit induced by endotoxin. Local application of capsaicin to the vagus nerve rather than application of capsaicin to the celiac ganglion significantly repressed endotoxin-induced delay in gastric emptying. Neither treatment modified the rate of gastric emptying in vehicle-treated animals. Blockade of CGRP receptors (CGRP 8-37, 100 microg/kg i.v.) did not alter gastric emptying in control animals but significantly prevented endotoxin-induced inhibition of gastric emptying. In contrast, a tachykinin receptor antagonist ([D-Pro2, D-Trp7.9]-substance P, 2 mg/kg i.p.) significantly reduced the rate of gastric emptying in control animals and did not modify the inhibitory effects of endotoxin. Adrenergic blockade with phentolamine (3 mg/kg i.p.) +/- propranolol (5 mg/kg i.p.) or muscarinic antagonism with atropine (0.1 mg/kg i.p.) failed to reverse the delay in gastric emptying induced by endotoxin. These observations indicate that endotoxin-induced delay in gastric emptying of a solid nutrient meal is mediated by capsaicin-sensitive afferent neurons.     

Motor activity of the rat duodenum in vivo: evidence for the existence of an atropine-resistant peristalsis

The motor activity of the proximal duodenum has been investigated by means of a balloon method in urethane-anaesthetized rats. A series of atropine- (1 mg/kg i.v.) or hexamethonium- (20 mg/kg i.v.) sensitive rhythmic contractions can be demonstrated in the rat duodenum which represents a peristaltic reflex mediated by intramural cholinergic neurons. The atropine-sensitive peristaltic reflex is transiently suppressed by intravenous DMPP (0.1 mg/kg) GABA (3 mg/kg) or noradrenaline (10 micrograms/kg). In rats pretreated with guanethidine (20 mg/kg s.c.) plus naloxone (2 mg/kg i.v.) and theophylline (2 mg/kg i.v.) a second type of peristaltic reflex which is atropine-resistant but hexamethonium-sensitive can be demonstrated. These findings indicate that in the rat small intestine a peristaltic activity can be sustained by both atropine-sensitive and atropine-resistant mechanism, which may explain failure of atropine to affect intestinal motility in conscious rats.