Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists.

We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)).

SCH 23390 affords protection against soman-evoked seizures in the freely moving guinea-pig: a concomitant neurochemical, electrophysiological and behavioural study.

We studied the role of striatal dopamine (DA) release in seizure activity evoked by the subcutaneous administration of the cholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman), in the guinea-pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the D(1)-like receptor antagonist SCH 23390 (0.5 mg kg(-1)) or the D(2)-like receptor antagonist sulpiride (30 mg kg(-1)).

Novel method of monitoring electroencephalography at the site of microdialysis during chemically evoked seizures in a freely moving animal.

This paper covers the design, development and operation of a novel piece of equipment, based around the CMA/12 guide probe (Carnegie Medicin, Sweden), which offers a low cost alternative for monitoring EEG at the site of microdialysis in a freely moving animal. This equipment is entirely based on commercially available parts, and thus can be easily replicated. Moreover, it is less intrusive than earlier models, offering advantages for experiments in which behavioural testing or chronic monitoring is required.

The effect of acute kainic acid treatment on mu-opioid receptors in rat brain.

There is evidence that acute exposure to kainic acid (KA) induces the release of endogenous ligands for opioid receptors and that mu-opioid agonists intensify KA-induced neurodegeneration. The aim of the present study was to investigate any acute toxic effects of KA upon mu-opioid receptors labelled with [3H]-DAMGO. 200-250 g rats were injected intraperitoneally with either saline or 16 mg/kg KA and brains were removed after 4 h.

The effect of acute kainic acid treatment on dopamine D2 receptors in rat brain.

Acute exposure to kainic acid (KA) induces neurochemical changes in dopaminergic systems in the brain and the aim of the present study was to investigate the acute toxicity of KA upon dopamine D2 receptors. Adult rats were injected intraperitoneally with either saline or 16 mg/kg KA. Brains were removed after 4 h.

Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro.

Alpha-dendrotoxin (alpha-DTx), a snake venom toxin which blocks several types of fast-activating voltage-dependent potassium channels, induces limbic seizures and neuronal damage when injected into the brain. The mechanisms underlying these convulsant and neuropathological actions are not fully understood. We have studied the effects of alpha-DTx on neurotransmitter release and electrical activity in rat hippocampal brain slices and the role of excitatory amino acid receptors in mediating these actions of the toxin.

Measurement of the oxime HI-6 after peripheral administration in tandem with neurotransmitter levels in striatal dialysates: effects of soman intoxication.

In the present study, the technique of microdialysis combined with tandem high-performance liquid chromatography was used to determine the striatal levels of HI-6 and neurotransmitters following peripheral administration of HI-6 (50 mg/kg i.m.) in conscious, freely moving rats.

Compared toxicity of the potassium channel blockers, apamin and dendrotoxin.

The central toxicities of two potassium ion channel blockers, apamin and alpha-dendrotoxin (DTx), have been compared. Both apamin and dendrotoxin injected intracerebroventricularly produced signs of poisoning, including tremor and ataxia; however, only DTx produced changes in brain electrical activity, with high voltage spikes and epileptiform activity and subsequent brain damage. DTx, but not apamin, increased the amplitude of evoked field potentials and caused repetitive firing of neurones in hippocampal slices.

Amphetamine-evoked dopamine release from guinea-pig striatum is potentiated by environmental stress, a need for habituation with microdialysis equipment.

The microdialysis technique has been successfully applied to a study of amphetamine-evoked dopamine release in the striatum of conscious, freely-moving guinea-pigs. Basal levels of dopamine in guinea-pig striatal dialysates were comparable with published data from studies in rats. There were marked differences in the relative proportions of the two main dopamine metabolites in the guinea-pig compared to those reported previously in the rat, suggesting differences in the fate of dopamine between the species.

Effect of acute physostigmine-hyoscine pretreatment on the neurochemical changes produced by soman in the guinea-pig.

The protective effects of two dose regimes of the organophosphate pretreatment combination, physostigmine and hyoscine, were assessed on the central neurochemical changes produced following soman intoxication. The lower dose combination (physostigmine 20 ?g/kg, hyoscine 10 ?g/kg, s.c.

Neurotransmitter changes in guinea-pig brain regions following soman intoxication.

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.

Cardiovascular, biochemical and hormonal changes during food-induced hypotension in chronic autonomic failure.

The cardiovascular, biochemical and hormonal responses to a standard test meal have been investigated in patients with chronic autonomic failure and normal subjects. In autonomic failure there was a rapid (within 15 min), substantial and prolonged fall in blood pressure after the meal. A marked fall in blood pressure also occurred after a liquid meal of similar composition and caloric content, with no change in blood pressure in age-matched subjects with normal autonomic function.

A comparison of the distribution of neurotransmitters in brain regions of the rat and guinea-pig using a chemiluminescent method and HPLC with electrochemical detection.

Six brain areas of rats and guinea-pigs, killed by microwave irradiation, were used for the concomitant measurement of the levels and regional distribution of cholinergic, biogenic amine, and amino acid neurotransmitters and metabolites. Acetylcholine (ACh) and choline (Ch) were quantified by chemiluminescence; noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites by HPLC with electrochemical detection (HPLC-EC); and six putative amino acid neurotransmitters by HPLC-EC following derivatisation. The levels and regional distribution of these transmitters and their metabolites in the rat were similar to those reported in previous studies, except that biogenic amine transmitter levels were higher and metabolite concentrations were lower.

Differential blood pressure and hormonal effects after glucose and xylose ingestion in chronic autonomic failure.

1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects.

Hypotensive and sedative effects of insulin in autonomic failure.

The haemodynamic responses to intravenous insulin (0.15 units/kg) were measured in five patients with chronic autonomic failure who were not receiving drug treatment. After the administration of insulin supine blood pressure fell steadily, with a substantial reduction even before the onset of hypoglycaemia.

The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure.

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst.

A comparison of the effects of three substance P antagonists on tachykinin-stimulated [3H]-acetylcholine release in the guinea-pig ileum.

The potencies of three tachykinin antagonists [D-Pro4,D-Trp7,9,10]SP(4-11), [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP(1-11) and [D-Arg1,D-Trp7,9,Leu11]SP(1-11) (spantide) against eledoisin were examined in the guinea-pig ileum myenteric plexus, where a continuous superfusion system was employed to examine evoked release of [3H]-acetylcholine [( 3H]-ACh]); effects on mechanical activity of the preparations were also measured. Eledoisin was chosen as the standard tachykinin agonist since the rank order of potency observed in evoking release was eledoisin, kassinin, substance P, physalaemin; on this basis is may be presumed that an 'SP-E' type receptor was involved in the release process. The two undecapeptide antagonists both significantly reduced the response to eledoisin (10 nM) as assessed by both [3H]-ACh release and mechanical activity which under these conditions was largely dependent on ACh release, and the response levels could be restored by increasing the concentration of eledoisin to 100 nM.

Comparison of potency of substance P and related peptides on [3H]-acetylcholine release, and contractile actions, in the guinea-pig ileum.

A range of tachykinins including substance P were studied for their ability to contract the guinea-pig ileum longitudinal muscle preparation on brief exposure (20S) to the peptides, and their ability to evoke the release of [3H]-acetylcholine (ACh) from previously labelled stores within the myenteric plexus. With respect to their immediate spasmogenic activity, none of the peptides differed greatly in potency from substance P. Atropine did not modify the response to the tachykinins suggesting that the release of ACh does not contribute to the contraction resulting from brief exposure to the peptides.

Inhibition of electrically induced twitch responses of the guinea-pig ileum by histamine.

Inhibition of twitch responses of the guinea-pig isolated ileum to low frequency electric stimulation (0.2 Hz) followed the interpolation of a dose of histamine left in contact for 30 sec. This post-histamine inhibition, which was dose related, was not affected by mepyramine or cimetidine and thus was not brought about by an action on known histamine receptors.

The effects of some dopamine antagonists on cholinergic mechanisms in the guinea-pig ileum.

1. Activation of prejunctional muscarinic and opiate receptors on cholinergic neurones of the guinea-pig ileum by acetylcholine (ACh) or morphine was seen as an inhibition of twitch responses to transmural electrical stimulation. These inhibitory responses were antagonised by metoclopramide and DL308-IT but no other antagonist used blocked the morphine responses apart from sulpiride in very high concentrations (100 muM and above).

Modulatory action on the twitch responses of the guinea-pig ileum of endogenous substances released by high frequency electrical stimulation.

Inhibition of twitch responses of the guinea-pig isolated ileum to low frequency electrical stimulation (0.2 Hz) followed the interpolation of a 30 sec period of high frequency electrical stimulation (HFS; 7.5 and 10 Hz).

Modulation by acetylcholine of the electrically-evoked release of [3H]-acetylcholine from the ileum of the guinea-pig.

1 Acetylcholine (ACh) stores within neurones of the myenteric plexus of the guinea-pig were labelled with [3H]-choline and the influence of unlabelled ACh, atropine, or atropine and unlabelled ACh on the electrically-evoked output of [3H]-ACh was evaluated. 2 Electrical transmural stimulation (5 Hz) of the ileum led to an increase in the output of [3H]-ACh over that released spontaneously. Superfusion with unlabelled ACh (6.

Release-modulating acetylcholine receptors in cholinergic neurones of the guinea-pig ileum.

1 Twitch responses of the guinea-pig ileum to electrical transmural stimulation (0.2 Hz) were smaller after a dose of acetylcholine (ACh) than before it. The magnitude of the post-ACh inhibition of twitch was dose-dependent.