Protection by 4-amino-hex-5-enoic acid (gamma-vinyl GABA) and hypobaric hypoxia against kainic acid neurotoxicity.

The behavioral effects following IP injection of kainic acid in rats could be cancelled with hypobaric hypoxia (8% O2 corresponding to 7000 m altitude) or with IP injections of 7-amino-hex-5-enoic acid at a dose of 0.9 g/kg-1. This protection may result from increased accumulations of GABA in brain tissues.

[Control of the regeneration of small pieces of the planarian Dugesia tigrina by cylic AMP and GMP nucleotides]. / Contrôle de la régénération de petits morceaux de planaire Dugesia tigrina par les nucléotides cycliques AMP et GMP

The effects on regeneration of cyclic nucleotides AMP and GMP were studied on small pieces of the planarian worm Dugesia tigrina. db cAMP, 8Br cGMP and substances acting on their metabolism were used in this work (aminophylline, insulin, imidazole). It seems that these second messengers play a role in a mechanism of regulation in which cGMP has a promotive action and cAMP an inhibitive one.

The role of monoamines in the behavioural effects of kainic acid in rats.

Male albino rats given as intraperitoneal injection of kainic acid (11 mg/kg) showed a behavioural syndrome of wet-dog shakes, vertical paddling and tonic convulsions followed by aphagia and aggressivity. The phase of wet-dog shakes, vertical paddling and convulsions was reduced by pretreatment with benserazide and alpha-methylparatyrosine at low doses, while FLA-63 and high doses at AMPT (greater than 200 mg/kg) were toxic together with kainic acid. The phase of aphagia was not influenced reliably by any of the pretreatments, while the phase of aggressivity was potentiated strongly by parachlorophenylalanine and slightly by reserpine and AMPT. The findings suggest that dopaminergic and serotoninergic functions play a role in effects of kainic acid on behaviour in rats.

[Toxic effects of essential oil of Cannabis sativa L. and main constituents on planarian (Dugesia tigrina) (author's transl)]. / Etude de la toxicité de l'huile essentielle de Cannabis sativa L. et de ses principaux constituants sur la planaire (Dugesia tigrina G.).

Regenerating pieces of planarian worms are able to absorbe insoluble substances deposited on the base of the vessels in which they are cultivated. This biological test was used to study the toxic effects of the essential oil of Cannabis sativa L. The hydrocarbons such as pinene (alpha and beta), caryophyllene and so on were not toxic. On the contrary caryophyllene oxide was highly toxic. It was not possible to detect any protection by 5-hydroxytryptamine as it was the case against delta 1-tétrahydro-cannabinol and cannabidiol.

Behavior and kainic acids differential behavioral and biochemical effects of kainic acid and allokainic acid injections in rats.

Using intraperitoneal injections, it was observed that kainic acid (KA) and its stereoisomer, allokainic acid (AKA), differ in their ability to produce wet-dog shakes (WDS), stereotypies and convulsions in Sprague-Dawley rats. KA induced this sequence of events for 5 hours after treatment while AKA had no effect even at much higher doses. On the other hand, both isomers induced sparring. KA caused also some significant changes in serotonin levels in hippocampus 6 days after injection while AKA did not. These findings suggest that WDS, stereotypies and convulsions depend on the position of the isopropenyl group in relation to the pyrrolidine ring of the molecule while sparring is not dependent on its spatial configuration.

Modulation of action of kainic acid on the behavior of rats by p-chlorophenylalanine and by gaba-mimetic drugs. Biochemical correlation between behavior and treatments.

Systemic injection of kainic acid (KA, 11 mg/kg i.p.) to male albino Sprague-Dawley rats produced a sequence of behavioral events: stereotypies, convulsions, aphagia and aggressiveness in the form of sparring at artificial night fall, as well as a decline in brain-Gaba and brain-dopamine (DA)-levels followed by an increase in DA-levels on days 6 and 10 after treatment. No notable variations in serotonin (5-HT) was observed. Pretreatments of rats with GABA-mimetic drugs (gamma-vinyl GABA, 900 mg/kg i.p.; THIP, 1 microgram/1 microliter/rat, i.c.v.) prevented the occurrence of convulsion, aphagia and aggressiveness. Systemic injection of p-chlorophenylalanine (PCPA) (300 mg/kg i.p.) induced aggressiveness in the form of sparring at night fall. Treatment with PCPA followed by injection of KA shifted mild aggressive behavior to a violent one in the form of biting and killing familiar rats. The findings suggest that KA-neurotoxicity is due in part to its effects on GABA- and DA-neurotransmissions. It is shown also that convulsions are induced by a decline in GABA-level while sparring is provoked by an enhancement in DA-level. Violent aggressiveness is induced by the additive disruptive effects on GABA- and 5-HT-neurotransmissions in PCPA + KA treated animals.

Time course relation between neurotoxic effects of kainic acid on behaviour and brain GABA-levels. Protection by gamma-vinyl GABA.

Administration of kainic acid (KA, 11 mg/kg i.p.) to rats produced a syndrome of abnormal behaviour (hyperexcitability, stereotypies, convulsions, aphagia and aggressivity) as well as a reduction in brain GABA levels during the first days after treatment. Pretreatments of rats with gamma-vinyl GABA (900 mg/kg) elevated brain GABA levels and prevented the occurrence of convulsions and aphagia. The findings suggest that KA neurotoxicity is due in part to its disruptive effects on GABA neurotransmission.