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Biomedical subjects

M G Corda

Publications and source records attributed to M G Corda.

At least 19 recordsLinked to original sources
PubMed1992

Decrease in GABAergic function induced by pentylenetetrazol kindling in rats: antagonism by MK-801.

The role of tau-aminobutyric acid (GABA)A receptors and of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors was studied in the pentylenetetrazol (PTZ) kindling model. The repeated administration of subconvulsant doses of PTZ (30 mg/kg i.p., 3 times a week for up to 10 weeks) produced chemical kindling in 80% of rats under treatment. PTZ kindling was associated with a decrease in GABA-mediated inhibition in the central nervous system. Thus, the binding of [3H]GABA, the binding of 35S-t-butylbicyclophosphorothionate and the GABA-stimulated uptake of 36Cl- were significantly decreased in the cerebral cortex of PTZ-kindled rats as compared with control rats chronically treated with saline. Moreover, PTZ-kindled rats showed a persistent increase in the sensitivity to the convulsant action of different GABA function inhibitors, such as isonicotinic acid hydrazide (120 mg/kg s.c.), picrotoxin (1.5 mg/kg i.p.), bicuculline (1.3 mg/kg s.c.), FG 7142 (N-methyl-beta-carboline-3-carboxamide; 20 mg/kg i.p.) and Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo-(1,5-a) (1,4)-benzodiaze pine-3-carboxylate; 20 mg/kg i.p.). The pretreatment with the noncompetitive NMDA receptor antagonist, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate; 0.1-1.0 mg/kg i.p., 40 min before each injection of PTZ], prevented in a concentration-dependent manner the development of kindling and the increase in the responsiveness to the convulsant effects of GABA function inhibitors observed in PTZ-kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Age-related decrease in the density of benzodiazepine recognition sites in the brain of the fresh water eel (Anguilla anguilla).

The binding parameters of benzodiazepine receptors labeled with [3H]flunitrazepam were investigated in the brain of male adult eels at the trophic phase (4 years old) and of male silver eels (6 year old ocean migrants). The density of [3H]flunitrazepam binding sites was significantly decreased (-26%) in the brain of silver eels compared with younger counterparts. In contrast, the apparent dissociation constant (Kd) was not significantly different in the two experimental groups. These results are discussed in terms of the possible involvement of stress, behavioral and environmental factors and age-related degenerative processes.

Aging↗
PubMed1991

MK-801 prevents chemical kindling induced by pentylenetetrazol in rats.

The repeated administration of pentylenetetrazol (PTZ) at a subconvulsant dose (30 mg/kg i.p., three times a week for nine weeks) produced kindling in 90% of rats under treatment. Pretreatment with the N-methyl-D-aspartate receptor antagonist, MK-801 (1 mg/kg i.p., 40 min before PTZ), prevented the behavioral manifestation (i.e. motor seizures) as well as the development of kindling. In fact, convulsions were not observed in rats pretreated with MK-801 either during the chronic PTZ administration or when challenged with PTZ three and 10 days after completion of the chronic treatment. The results suggest an involvement of excitatory amino acid neurotransmission in PTZ kindling.

Amino Acids↗
PubMed1991

Pentylenetetrazol-induced kindling in rats: effect of GABA function inhibitors.

The repeated administration of subconvulsant doses of pentylenetetrazol (PTZ) produced a progressive sensitization to the effects of this compound (i.e., chemical kindling) in the rat. A very similar time-course for PTZ-induced kindling was observed using two different treatment schedules: 1) one injection every day (30 mg/kg, IP), and 2) one injection (30 mg/kg, IP) every second day. When these treatment schedules were used for eight consecutive weeks, more than 80% of the rats displayed convulsions by the end of treatment. In contrast, only 20% of the rats were sensitized if PTZ was administered twice daily at the dose of 15 mg/kg, IP. The increased sensitivity to the convulsant effect of PTZ was still present one year after completion of the chronic treatment. Moreover, rats kindled with PTZ showed an enhanced susceptibility to convulsions induced by different inhibitors of central GABAergic function, such as the chloride channel blocker picrotoxin, the benzodiazepine receptor ligands FG 7142 and Ro 15-4513, and the inhibitor of GABA synthesis isoniazid. In contrast, the sensitivity to the convulsant action of the glycine receptor antagonist strychnine was unchanged by repeated PTZ administration. It is suggested that kindling produced by PTZ may be associated with a persistent reduction in the inhibitory function of the GABAergic system in the brain.

Animals↗
PubMed1991

MK-801 prevents the decrease in 35S-TBPS binding in the rat cerebral cortex induced by pentylenetetrazol kindling.

Chemical kindling was induced in the rat by chronic treatment with pentylenetetrazol (PTZ, 30 mg/kg, IP, three times a week for eight weeks). PTZ kindling was associated with a reduction in central GABAergic function, as reflected by a significant decrease in the density of 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in the cerebral cortex. The pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (1 mg/kg, IP, 40 min before each PTZ injection) prevented the development of kindling as well as the reduction in 35S-TBPS binding. The results suggest that NMDA receptors may play a role in the alterations of GABAergic function observed in PTZ-kindled rats.

Animals↗
PubMed1990

Proconflict effect of ACTH1-24: interaction with benzodiazepines.

The intracerebroventricular injection of ACTH1-24 (0.1-10 micrograms) produced a dose-dependent decrease of punished licking periods in the conflict test in rats. The same treatment failed to modify unpunished behavior. A similar effect was produced by alpha-MSH (0.25-5 micrograms), whereas ACTH4-10 and ACTH11-24 were ineffective in doses up to 10 micrograms. The proconflict effect of ACTH1-24 was completely antagonized by diazepam (1.5 mg/kg IP) and partially by the benzodiazepine receptor antagonist Ro 15-1788 (5 mg/kg IP). The results are in line with a possible "anxiogenic" action of ACTH1-24.

Adrenocorticotropic Hormone↗
PubMed1990

GABAergic and dopaminergic transmission in the rat cerebral cortex: effect of stress, anxiolytic and anxiogenic drugs.

Benzodiazepines produce their pharmacological effects by regulating the interaction of GABA with its recognition site on the GABAA receptor complex. In fact, the anxiolytic effect of benzodiazepines may be considered the consequence of the activation of the GABAA receptors induced by these drugs. On the contrary, beta-carboline derivatives which bind with high affinity to benzodiazepine recognition sites modulate the GABAergic transmission in a manner opposite to that of benzodiazepines. Thus, these compounds reduce the function of the GABA-coupled chloride channel and produce pharmacological effects (anxiogenic, proconvulsant and convulsant) opposite to those of benzodiazepines. Taken together, these data strongly indicate that the GABAA receptor complex plays a major role in the pharmacology, neurochemistry and physiopathology of stress and anxiety. This conclusion is further supported by the finding that the function of the GABAA/benzodiazepine receptor complex may be modified by the emotional state of the animals before sacrifice. Accordingly, using an unstressed animal model, the 'handling-habituated' rats, it has been demonstrated that stress, like anxiogenic drugs, decreases the function of GABAA receptor complex, an effect mimicked by the in vivo administration of different inhibitors of GABAergic transmission and antagonized by anxiolytic benzodiazepines. Moreover, a long-lasting down regulation of GABAergic synapses can be obtained after repeated administration of anxiogenic, proconvulsant and convulsant negative modulators of GABAergic transmission. The latter finding further suggests that GABAergic synapses undergo rapid and persistent plastic changes when the GABAergic transmission is persistently inhibited. Finally, the evidence that the activity of mesocortical dopaminergic pathways is altered in opposite manner by drugs that either inhibit or enhance the GABAergic transmission indicates that GABA has a functional role in regulation of dopaminergic neurons in the rat cerebral cortex. Altogether these results suggest that cortical GABAergic and dopaminergic transmission play a major role in the pharmacology, neurochemistry and pathology of the emotional states and fear.

Animals↗
PubMed1990

Decrease in the function of the gamma-aminobutyric acid-coupled chloride channel produced by the repeated administration of pentylenetetrazol to rats.

The acute administration of pentylenetetrazol (PTZ; 25-75 mg/kg i.p.) failed to modify the specific binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to membrane preparations from the cerebral cortex of the rat. In contrast, the repeated administration of PTZ (30 mg/kg i.p., three times a week for 12 weeks) reduced by 26% the density of [35S]TBPS binding sites without modifying the dissociation constant. This effect was observed 3 days after the last PTZ administration. A parallel reduction of gamma-aminobutyric acid (GABA)-stimulated 36Cl- uptake was measured in the cerebral cortex of PTZ-treated rats 3 days after the last injection. The repeated administration of PTZ produced sensitization to the drug, or chemical kindling. In fact, no convulsions were observed in the first week of treatment, but all the animals became sensitized to PTZ by the 12th week. The results are consistent with the hypothesis that chronic treatment with PTZ at a subconvulsant dose causes a decrease in GABA-coupled chloride channel activity that may be related to the chemical kindling produced by this compound.

Animals↗
PubMed1979

Decrease of cyclic GMP in cerebellar cortex by intrastriatal (--)-sulpiride.

Intraperitoneal administration of (--)-sulpiride (12 to 50 mg/kg) produced a dose-related decrease in cGMP content in cerebellar cortex, while the (+)-sulpiride (10 microgram), but not after intracerebellar injection. These findings support the contention that (--)-sulpiride modifies cerebellar cGMP levels through and action on striatal dopamine receptors.

Animals↗
PubMed1978

Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone.

The intraventricular injection of methionine-enkephalin (50 to 100 micrograms) or [d-Ala2]-methionine-enkephalinamide (1.5 to 12 micrograms), a synthetic enkephalin analog resistant to enzyme degradation, caused a marked dose-dependent increase in dihydroxyphenylacetic acid and homovanillic acid concentrations in the rat striatum. The [d-Ala2] analog increased the accumulation of dopa in the striatum after aromatic amino acid decarboxylase inhibition, indicating that it increased dopamine synthesis. At the highest doses used both enkephalins failed to modify brain serotonin metabolism. The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy. The stimulant effect of the [d-Ala2] analog on dopamine synthesis in the striatum persisted after destruction of striatal postsynaptic dopamine receptors with kainic acid. The biochemical and behavioral effects of enkephalins were prevented by naloxone, a specific narcotic antagonist. The results indicate that enkephalins stimulate dopamine synthesis by an action on opioid receptors localized on dopaminergic nerve terminals.

3,4-Dihydroxyphenylacetic Acid↗