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Biomedical subjects

G Nisticò

Publications and source records attributed to G Nisticò.

173 records · Page 10Linked to original sources

Panic-like attack induced by microinfusion into the locus coeruleus of antagonists and inverse agonists at GABAA-receptors in rodents.

The microinfusion of drugs inhibiting GABA-ergic transmission into the locus coeruleus (LC) of rats and mice produced a dramatic pattern of behavioural stimulation accompanied by marked electrocortical (ECoG) desynchronization. In rats, unilateral microinfusion into the LC of bicuculline (0.5-4 pmol) produced dose-dependent behavioural stimulation culminating in a panic-like attack, ECoG desynchronization and marked changes in ECoG spectrum power. These effects were prevented by a pretreatment into the same site with muscimol. Similarly, in mice, the microinfusion of ethyl-beta-carboline-3-carboxylate (beta-CCE, 4.1 nmol) into the LC of C57BL/6 mice produced an intense state of behavioural stimulation accompanied by intense stereotyped movements and increased excitability to external stimuli; these effects were prevented by prior microinfusion of diazepam or flumazenil into the same site. In conclusion, the present experiments show that in rodents drug manipulations leading to a decrease in the activity of GABA-benzodiazepine receptor complex in the LC are responsible for the occurrence of panic-like attacks.

Animals↗

Evidence that paraquat is able to cross the blood-brain barrier to a different extent in rats of various age.

The brain levels of paraquat were determined in rats of different age after systemic administration of several doses of the herbicide. Two week-, 3, 12 and 24 month-old rats were subcutaneously injected with paraquat (1, 2.5 and 5 mg/kg) and sacrificed 1 h later. A method based on ion-pair solid-phase extraction and reversed-phase high performance liquid chromatography was used to measure brain paraquat concentrations. The acute administration of paraquat resulted in dose-related and age-dependent brain concentrations of the herbicide, higher brain levels being detected in 12 and 24 month-old rats in comparison to young animals (3 month-old). In comparison with 3 month-old rats, higher concentrations of paraquat were also observed in the brain of 2 week-old animals. The present results demonstrate that in rats systemic treatment with paraquat gives rise to higher brain concentrations of this herbicide in very young and old rats in comparison with 3-month-old animals. This suggests that age-dependent changes in blood brain barrier permeability may account for these differences.

Aging↗

A decrease in guanylate cyclase activity in some tissues of C3H/HeJ mice with retinal dystrophy.

Guanylate cyclase activity was assayed in homogenates, in particulate and soluble fractions from retina, cerebellum, cerebral cortex and adrenal gland of adult C3H/HeJ mice with a dystrophic retinopathy. In comparison to control mice (DBA/1J), in C3H/HeJ strain a significant decrease in guanylate cyclase activity occurred in homogenates from retina, cerebellum and adrenal gland. In particular a significant decrease was found in particulate fraction of retina, in the soluble fraction of cerebral cortex and cerebellum and in both fractions of the adrenal gland. In contrast to the retina and cerebellum where guanylate cyclase activity in homogenates was found significantly decreased both in the male and female, in the cerebral cortex guanylate cyclase decreased in both sexes although in female this was more marked.

Adrenal Glands↗

Electrocortical desynchronization after microinfusion of kainic acid into the locus coeruleus in rats.

Receptors for the endogenous excitatory amino acid, 1-glutamate, occur in the rat locus coeruleus (LC), an area of the brain involved in the control of sleep/arousal mechanisms and other behavioral functions. However, the functional role of this neurotransmitter system in the LC has yet to be clarified. Therefore, to address this question we have studied the gross behavioral changes and the effects on the electrocortical (ECoG) spectrum power in rats receiving focal injections into the LC of kainic acid, an agonist at the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor subtype. Unilateral injection of kainic acid (25, 50, 100 and 200 pmol) into the rat LC produced contralateral turning, circling and stereotypes; these effects were accompanied by dose-dependent ECoG desynchronization and by a significant decrease in total voltage power and in 6-9, 9-12 and 12-16 Hz bands of the ECoG spectrum. A pretreatment (15 min before) with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 and 100 pmol), a competitive non-NMDA receptor antagonist, or with dizocilpine meleate (MK-801) (1 pmol) and 3-(2-carboxy-piperazine-4-yl)-1-propenyl-1-phosphonic acid) (CP-Pene) (10 pmol), two selective NMDA receptor antagonists, injected directly into the LC, abolished the behavioral and ECoG spectrum power effects typically elicited by kainic acid (50 pmol). Similar results were observed in rats pretreated with diazepam (0.5 mg/kg given i.p. 15 min before kainic acid).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence that CRH microinfused into the locus coeruleus decreases cell-mediated immune response in rats.

Rat/human-corticotropin-releasing hormone (CRH) microinfused unilaterally into the locus coeruleus (LC) of awake, chronically cannulated rats produced intense behavioral stimulation accompanied by a marked decrease of the proliferative response of splenocytes to Con A and LPS and natural killer activity. These effects were specifically prevented by prior administration into the same site of the CRH antagonist (alpha-helical CRH [9-41]). The present results confirm that a strict relationship exists between the CNS and cell-mediated immunity; in addition, they also indicate that CRH produces its behavioral and immune changes by an interaction with specific receptors and that one of the main sites through which CRH exerts these effects is represented by the LC.

Animals↗

Systemic administration of pramiracetam increases nitric oxide synthase activity in the cerebral cortex of the rat.

The effect of systemic administration of pramiracetam on neuronal type nitric oxide synthase (NOS) activity and NOS mRNA expression were studied in the hippocampus and cerebral cortex in rats. A dose of 300 mg/kg (i.p.) of this nootropic produced an approximately 20% increase in NOS activity in rat brain cortical homogenates but not in hippocampal homogenates; no significant changes were observed in NOS mRNA expression in the cortex and hippocampus. A lower dose of pramiracetam (100 mg/kg i.p.) was ineffective on NOS mRNA expression and enzyme activity. Interestingly, administration of pramiracetam (300 mg/kg i.p.) in rats pretreated (24 h before) with lithium chloride (LiCl) (3 mEq/kg i.p.) yielded a 40% increase in cortical NOS activity. However, in LiCl-pretreated rats this nootropic failed to affect cortical NOS mRNA expression; LiCl (3 mEq/kg i.p.) given alone produced no effect. In conclusion, the present data demonstrate that pramiracetam given alone or in combination with LiCl increases NOS activity in brain cortical homogenates of rats and this may contribute to the mechanisms underlying learning and memory improvement produced by this nootropic.

Animals↗