Production of limbic motor seizures and brain damage by systemic and intracerebral injections of paraquat in rats.

The behavioural and neuropathological effects of both systemic and intrahippocampal injections of paraquat dichloride (1,1'-dimethyl 4,4'-bipyridinium dichloride) were studied in rats. Paraquat (0.1-1.

Glutamate transmission is involved in the mechanisms of neuronal degeneration produced by intrahippocampal tetanus toxin in rats.

Tetanus toxin (TT) blocks GABA-mediated inhibitory neurotransmission in the mammalian CNS via selective inhibition of transmitter release. The loss of central inhibition produces an excitatory focus resembling human limbic epilepsy. We now report that the net excitation caused by an unopposed action of glutamic acid may also produce neuronal degeneration in the rat brain.

Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats.

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1 mumol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage.

Production of seizures and brain damage in rats by alpha-dendrotoxin, a selective K+ channel blocker.

alpha-Dendrotoxin (Dtx), a snake polypeptide, increases neuronal excitability by blocking certain fast-activating, voltage-dependent K+ channels. Thus, the behavioural, electrocortical (ECoG) and neuropathological effects of Dtx, injected into rat brain areas, were studied. A unilateral injection of 35 pmol of Dtx into the CA1 hippocampal area or the dendate gyrus (DG; upper blade) immediately produced motor and ECoG seizures, followed at 24 h by multi-focal brain damage and significant neuronal loss.

Tacrine-induced seizures and brain damage in LiCl-treated rats can be prevented by N omega-nitro-L-arginine methyl ester.

The effects of tacrine (5 mg/kg i.p.), a potent acetylcholinesterase inhibitor, were studied in rats pretreated (24 h beforehand) with a single dose (12 mEq/kg i.

Epileptogenic effects of skin extracts from the Australian frog Pseudophryne coriacea after intracerebral microinfusion in rats.

The behavioural and electrocortical (ECoG) effects induced by a methanol extract of the skin of the Australian frog Pseudophryne coriacea, directly microinjected into several areas of the brain, were studied in freely moving rats. Administration of the P. coriacea extract (5, 10, 15 and 20 micrograms) into the dorsal hippocampus produced a dose-dependent and reversible behavioural stimulation and ECoG spikes lasting 20-140 min.

Muscarinic receptor activation induces a prolonged post-stimulus afterdepolarization with a conductance decrease in guinea-pig olfactory cortex neurones in vitro.

The persistent excitation of guinea-pig olfactory cortical neurones in vitro by the muscarinic agonist oxotremorine-M (OXO-M) was investigated. In OXO-M (10-20 microM), a slowly-decaying afterdepolarization (sADP) accompanied by sustained repetitive firing was induced following a long depolarizing stimulus. The corresponding slow inward current (IADP) revealed under voltage clamp behaved like a K(+)-mediated tail current, but was associated with a decreased membrane conductance.

High vulnerability of dentate granule cells to the neuropathological effects induced by intrahippocampal injection of tetanus toxin.

The behavioural and neuropathological effects of tetanus toxin, injected into the dentate gyrus, were studied in rats. The monolateral injection of a single dose (1000 mouse minimum lethal doses, MLDs; n = 14 rats) of tetanus toxin produced time-dependent behavioural stimulation. Wet-dog shakes and facial stereotypy were observed 3-4 days after the injection, culminating 4-5 days after treatment, in "limbic motor seizures".

Muscarinic inhibition of excitatory neurotransmission in guinea-pig olfactory cortex slices: weak antagonism by M3-muscarinic receptor antagonists.

Dose-dependent depression of the electrically evoked surface-negative field potential (N-wave) produced by bath-superfusion of carbachol was measured in guinea-pig olfactory cortex slices maintained in vitro. The possible involvement of M3 (smooth muscle/glandular) type muscarinic receptors in partly mediating this response was investigated by testing the effectiveness of the muscarinic M3 receptor antagonists hexahydro-sila-difenidol (HHSiD) and p-fluoro-hexahydro-sila-difenidol (p-F-HHSiD). Low doses of HHSiD (10-100 nM) or p-F-HHSiD (up to 1 microM), pre-applied for 30 min, produced no obvious antagonism of carbachol responses.

Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide.

Increasing evidence suggests a neurotransmitter role for NO in the mammalian CNS. We have now studied the behavioural and electrocortical (ECoG) profile of rats injected into the lateral cerebral ventricle (ICV) with L-arginine (L-arg), the endogenous donor of the guanidino group from which NO physiologically originates. Rats treated with L-arg (up to 300 micrograms) showed behavioural stimulation, ECoG desynchronization with occasional isolated high voltage spikes but not motor seizures.

Hippocampal damage produced by tetanus toxin in rats can be prevented by lesioning CA1 pyramidal cell excitatory afferents.

The neuropathological effects induced by tetanus toxin (TT) bilaterally microinjected into the hippocampus were studied in rats bearing a surgical unilateral lesion of the Schaffer collaterals. TT (1000 mouse minimum lethal doses, MLDs; n = 5 rats) produced neurodegeneration in the CA1 pyramidal cell layer in the unlesioned side of the hippocampus ten days after injection. By contrast, the injection of TT into the lesioned hippocampus produced no degeneration.

Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus.

1. The behavioural and neuropathological effects of tetanus toxin, microinjected directly into the hippocampus, were studied in rats. 2.

Different profile of electrocortical power spectrum changes after micro-infusion into the locus coeruleus of selective agonists at various opioid receptor subtypes in rats.

1. The effects of various opioid receptor agonists given directly by means of a chronically implanted cannula into the locus coeruleus (LC) on behaviour and ECoG activity, continuously analysed, and quantified as total power spectrum (0-16 Hz) and in preselected frequency bands (0-3; 3-6; 6-9; 9-12 and 12-16 Hz), were studied in rats. 2.

Behavioural and neuropathological effects produced by tetanus toxin injected into the hippocampus of rats.

The behavioural effects of tetanus toxin, injected into the rostral hippocampus, have been studied in rats. A single dose (1000 mouse minimum lethal doses; n = 10) of the toxin produced tail rigidity, hunched back and sound- and touch-evoked stimuli, 48 hr after the injection in all rats treated and these culminated in generalized convulsions 5-7 days later. Seizures were also observed 4 days after the injection of 2000 MLDs (n = 10), whereas a dose of 500 MLDs (n = 10) was ineffective.

Muscarinic suppression of the evoked N-wave by oxotremorine-M recorded in the guinea-pig olfactory cortex slice.

The effect of the muscarinic agonist oxotremorine-M has been studied on the surface-negative field potential (N-wave) evoked by orthodromic stimulation of the lateral olfactory tract in slices of guinea-pig olfactory cortex. Bath-application of oxotremorine-M (5-80 microM) or carbachol (10-300 microM) produced a reversible depression of the N-wave amplitude without affecting the lateral olfactory tract compound action potential. Oxotremorine-M was approximately 5 times more potent than carbachol in this respect, and the effects of both agonists were competitively blocked by telenzepine (5-100 nM), a selective M1-receptor antagonist.

Tetanus toxin produces neuronal loss and a reduction in GABAA but not GABAB binding sites in rat hippocampus.

The neuropathological effects of tetanus toxin, microinjected in the rat CA1 hippocampal area, were studied by using a microscopical and autoradiographical approach. Tetanus toxin produced a dose- and time-dependent neuronal loss in the CA1 area accompanied by a reduction in the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to GABAA but not GABAB sites in the pyramidal cell layer.

Age-dependent ECoG spectrum power alterations are reduced by phosphatidylserine in rats.

The present experiments were carried out in order to characterize the changes in ECoG spectrum power occurring in old compared with young rats. In addition, it was planned to ascertain whether chronic treatment with phosphatidylserine affected possible ECoG changes occurring in aged animals. In comparison to 3 months-old rats, the ECoG activity of 13-15 months-old rats showed spontaneous single or bursts of monophasic and biphasic spikes.

Inhibition by pertussis toxin of the soporific effects induced by stimulation of dopamine D2 autoreceptors in the ventral tegmental area in rats.

The behavioural and ECoG spectrum power effects of agonists at dopamine D2 autoreceptors, both after systemic or intracerebral administration, were studied in rats. It was shown that the bilateral injection of apomorphine or (+) 3PPP (0.1, 0.

Effects of pertussis toxin on the behavioural and ECoG spectrum changes induced by clonidine and yohimbine after their microinfusion into the locus coeruleus.

1. Pertussis toxin, a substance which interferes selectively with receptor-mediated signal transduction mechanisms, was injected into the locus coeruleus of rats 1, 2, 3, 6 or 10 days before the microinjection of clonidine or yohimbine into the same site. 2.

Microinfusion of clonidine and yohimbine into locus coeruleus alters EEG power spectrum: effects of aging and reversal by phosphatidylserine.

1. The behavioural and electrocortical (ECoG) power spectrum effects of clonidine, and yohimbine, an agonist and an antagonist at alpha 2-adrenoceptors, after their unilateral microinfusion into the rat locus coeruleus (LC) in young (50-70 days old) and old (13-15 months old) rats were studied. 2.

Ventral tegmental area: site through which dopamine D2-receptor agonists evoke behavioural and electrocortical sleep in rats.

1. In freely moving rats the effects on behaviour and electrocortical (ECoG) spectrum power of some dopamine agonists, i.e.

Behavioural and ECoG spectrum power effects after intraventricular injection of drugs altering dopaminergic transmission in rats.

In rats with cannulae permanently implanted into the third cerebral ventricle, the effects of different pharmacological manipulations affecting dopaminergic mechanisms, were studied on behaviour and electrocorticographic (ECoG) activity, continuously quantified in its spectrum power. The intraventricular injection (0.1-1 nmol) of (-)3PPP[3-(3-hydroxyphenyl) N-n-propylpiperidine], a specific agonist at dopamine (DA) autoreceptors, produced dose-dependent behavioural sedation or sleep and an increase in ECoG spectrum power, with a predominant increase in the lower frequency bands.