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Biomedical subjects

G Racagni

Publications and source records attributed to G Racagni.

At least 163 records · Page 9Linked to original sources
PubMed1984

Behavioural responsiveness to muscimol and apomorphine 2 months after prolonged treatment with estradiol in rats.

Two months after prolonged administration of estradiol (ES) in female rats the behavioural responsiveness to muscimol, a GABA receptor stimulating agent, and to apomorphine, a dopamine receptor agonist, was significantly altered. In particular, the decrease in locomotor activity induced by a challenge dose of muscimol (0.5-1 mg/kg) was significantly attenuated in ES-pretreated animals. Conversely, the intensity of stereotyped behaviour elicited by a challenge dose of apomorphine (1 mg/kg) was significantly increased in ES-pretreated rats. The behavioural alterations in the response to muscimol and apomorphine presumably result from the production of central GABA receptor subsensitivity and dopamine receptor supersensitivity respectively, induced by the prolonged ES administration.

Animals↗
PubMed1984

Regulation of prolactin secretion during suckling: involvement of the hypothalamo-pituitary GABAergic system.

Previous results demonstrated that GABA exerts a dual control on PRL secretion, one excitatory mediated in part by the impairment of the tubero-infundibular dopaminergic (TIDA) system function, the other inhibitory occurring at the level of the anterior pituitary (AP), where 3H-GABA and 3H-Muscimol (3H-M) recognition sites have been described. This report provides evidence for a physiological role of the tubero-infundibular GABAergic system (TI-GA-BA) on PRL secretion in the rat. In lactating rats separated for 4 h from their pups reinstitution of suckling for different periods resulted in an increase either in glutamic acid decarboxylase (GAD) activity in the mediobasal hypothalamus (MBH) or in AP-GABA content. Dynamic changes of the GABAergic function in the MBH-AP system seemed to have a certain degree of specificity because suckling did not affect GAD activity in the caudate nucleus. In lactating rats 2, 4, 8 and 24 h after removal of the offsprings AP-GABA concentrations and plasma PRL titers significantly decreased with respect to values present in rats never separated from their pups. Since it has been demonstrated that the PRL lowering effect of GABA is a receptor-mediated event, we have investigated the plasticity of AP-GABA receptors during suckling. The inhibitory action of GABA seems to be mediated mainly by the activation of the high affinity binding sites. This proposition is supported by the fact that in lactating rats, where only the high affinity receptor population is present, M was still able to decrease significantly plasma PRL concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Prolactin control by the tubero-infundibular GABAergic system: role of anterior pituitary GABA receptors.

Anterior pituitary (AP) GABA receptors have been shown to play a functional role in the inhibitory control of prolactin (PRL) secretion by this amino acid. However, the physiological significance and the pharmacological characteristics of these receptors have yet to be determined. In normal male rat AP's incubated in vitro, GABA (10(-6) M) is effective in decreasing PRL release only when incubated in the presence of ethanolamine-O-sulphate (EOS), a potent GABA-transaminase (GABA-T) blocker. The failure of GABA alone to inhibit PRL release in vitro could be explained by the rapid degradation of the amino acid when added to the medium by AP-GABA-T. Central nervous system (CNS)- and AP-GABA receptors present similar affinity constants when evaluated by Scatchard analysis. However, displacement studies show that AP-GABA receptors have 10- and 100-times less affinity for muscimol (M), a GABA agonist, and for bicuculline, a GABA antagonist, respectively, than have GABA receptors. The low affinity of the agonist towards the AP receptors could also account for the relatively poor sensitivity of lactotrophs to GABA-mimetic compounds. Failure of chronic treatment with aminooxyacetic acid, a GABA-T inhibitor, to modify the PRL-lowering effect of GABA-mimetic compounds, despite the decrease in the number of AP-GABA receptors, indicates that in normal conditions only a reduced number of receptors are operative. These studies of AP-GABA receptors provide insight for a better understanding of the mechanisms involved in the regulation of PRL secretion by the hypothalamic GABAergic system.

Animals↗
PubMed1984

Biochemical and immunochemical studies on the GABAergic system in the rat fallopian tube and ovary.

gamma-Aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) activities were measured in the ovary and the Fallopian tube of rats and compared with brain values. GABA levels in the Fallopian tube were about twice as high as in the brain, while in the ovary they represented only about 5% of the amino acid content of the CNS. In vitro decarboxylation of glutamate, measured via CO2 formation, occurred both in the Fallopian tube and in the ovary. These two organs contained, respectively, 10% and 1% of brain GAD activity. However, the actual formation of GABA from glutamate in a high-speed supernatant was detectable only in the Fallopian tube, where it represented about 5% of brain GAD activity. In contrast with the enzyme present in ovary, liver, anterior pituitary, and kidney, that in the Fallopian tube was quantitatively precipitated by a specific antiserum directed against rat neuronal GAD. Moreover, subcutaneous transplantation resulted in a quantitative decrease of both GABA levels and GAD activity in the Fallopian tube while no change occurred in the ovary, and vagus nerve section induced a 50% decrease of GAD activity in the Fallopian tube, although GABA levels were not significantly altered. The findings suggest an extrinsic GABAergic innervation in the rat Fallopian tube but not in the ovary.

Animals↗
PubMed1984

Behavioural and biochemical effects in C57BL/6J mice after a prolonged treatment with the delta-opiate antagonist ICI 154129.

A long term treatment with the delta-selective opiate antagonist NN-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129) produces an increase in the number of delta-opiate binding sites, whereas the same treatment with the non selective opiate antagonist naloxone results in an enhancement of both mu- and delta-binding sites. This biochemical effect in naloxone-pretreated mice is paralleled by a more pronounced increase in locomotor activity induced by a challenge dose of morphine. In contrast, no difference in the effect of morphine was seen in ICI 154129-pretreated mice with respect to control. These data suggest that the locomotor response to morphine in C57 mice is not mediated through delta-opiate receptors.

Adrenergic alpha-Antagonists↗
PubMed1984

Daily fluctuations in the activity of the tuberoinfundibular GABAergic system and plasma prolactin levels.

In view of the role exerted by gamma-aminobutyric acid (GABA) in the control of prolactin (PRL) secretion the circadian periodicity of hypothalamo-pituitary GABAergic activity and PRL secretion was evaluated in adult male rats to ascertain if a meaningful correlation between biochemical and endocrine indices may be evidenced. Anterior pituitary and median eminence GABA concentrations peaked during the late afternoon hours (18.00 h), while the glutamic acid decarboxylase activity reached higher concentrations at 15.00 h. Plasma PRL presented two circadian surges at 15.00 h and at midnight. Although the changes of GABA in the hypothalamo-pituitary complex and the PRL surges did not show a close temporal relation, the possibility may be considered that GABA circadian changes occurred as a delayed response to PRL circadian surges. However, it cannot be excluded that changes in the biochemical indices could be related to other neuroendocrine events.

Animals↗
PubMed1983

Behavioural changes after acute and chronic administration of typical and atypical antidepressants in rats: interactions with reserpine.

Acute administration of desipramine, mianserin and viloxazine produces a significant decrease of locomotor activity in rats. Conversely, the locomotion of rats receiving the antidepressants for a prolonged period of time is not modified with respect to control animals. Moreover, the reserpine-induced decrement of locomotion is not influenced by chronic treatment with any of the antidepressants used in the present study. Since tolerance develops rapidly to these behavioural effects they may be indicative of compensatory changes in neuronal systems which may occur during prolonged antidepressant treatment.

Animals↗
PubMed1983

Cyclic nucleotides in experimental and human brain tumors.

It is well known that the system of cyclic nucleotides plays an important role in cell differentiation and proliferation. Cyclic AMP is capable of stimulating cell growth, and cyclic GMP is thought to control cell division and growth. The authors measured adenylcyclase activity (AC) and cGMP content in the tumor latency period and in early neoplastic proliferations in rats with brain tumors induced by transplacental ethylnitrosourea (ENU). AC activity, which is high during the first days of life, decreases until it reaches, at the 60th day, levels lower than those in control animals. Cyclic GMP, on the contrary, increases during the first month in treated animals and remains consistently higher than controls up to the 45th day. In fully developed experimental brain tumors (mixed gliomas, isomorphic and polymorphic oligodendrogliomas) the percentage of reduction in AC activity is significantly higher. AC activity was measured also in human tumoral tissue. In malignant tumors it is markedly lower than in benign tumors. In the same patients cAMP in the cerebrospinal fluid was measured with results similar to those obtained in tissues. These findings confirm that the system of cyclic nucleotides is implicated in all the developmental phases of brain tumors and therefore may reveal how research can clarify the first transformations of tumoral cells.

Adenylyl Cyclases↗
PubMed1983

Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

Animals↗
PubMed1983

The influence of early postnatal treatment with haloperidol on the effects induced by small and large doses of apomorphine on locomotion of adult rats.

Chronic administration of haloperidol (0.5 mg/kg, s.c.) during early postnatal life did not modify the effects produced by a small dose of apomorphine (0.02 mg/kg, s.c.) on the locomotor activity of adult rats; conversely, the reduction of locomotion induced by a large dose of apomorphine (1 mg/kg, s.c.) was much more kared in haloperidol-pretreated rat than in saline-pretreated ones. The differential ontogeny of dopamine auto- and postsynaptic receptors could be partly responsible for the different influence of postnatal treatment with haloperidol on the responsiveness of the adult to small and large doses of apomorphine.

Animals↗
PubMed1983

Temporal sequence of changes in central noradrenergic system of rat after prolonged antidepressant treatment: receptor desensitization and neurotransmitter interactions.

It has been shown that different receptor components may be involved in the adaptive changes occurring in noradrenergic (NE) neurones after prolonged periods of exposure to antidepressant drugs. In this report the desensitization of NE-coupled adenylate cyclase (NE-AC). beta-adrenergic receptors and [3H]imipramine ([3H]-IMI) or [3H]desipramine ([3H]-DMI) binding sites have been temporally correlated with in vivo changes of NE utilization. Normetanephrine (NMN) was measured as indicator of NE synaptic events involved in antidepressant action. Concentrations of normetanephrine were increased after acute desipramine (DMI), viloxazine and mianserin administration. Following 3 days of treatment, the antidepressant-induced increase of normetanephrine became tolerant and NE neurones were resistant to the antidepressant effect until the 15th day of treatment. After two weeks, DMI elicited a significant decrease in the content of normetanephrine. A different pattern of changes has been found in the temporal modification of [3H]-IMI recognition sites, beta-adrenoceptors and NE-AC activity after chronic DMI treatment. Binding sites and receptors were down regulated after 10 days of treatment preceding the decrease in normetanephrine content. No down-regulation was observed in [3H]-DMI binding sites. Studies on the effects of antidepressants during brain maturation revealed that the mechanisms which cause desensitization of beta-receptors and [3H]-IMI binding sites appear in the early stages of postnatal life. Since [3H]-IMI and [3H]-DMI recognition sites have been shown to be located on serotonergic (5-HT) and noradrenergic neurones respectively, the interactions between NE and 5-HT neurones could represent possible mechanisms implicated in receptor desensitization. The experiments presented involving lesions of 5-HT neurones have clearly demonstrated that NE release in rat cerebral cortex is under a tonic serotonergic influence. Alterations in the chemico-physical properties of the synaptic membranes might be also taken in consideration for the mechanisms underlying receptor modulation. In fact, evidence is provided that in neural tissue phospholipid methylation can be affected. In conclusion, the temporal sequence of changes in cortical noradrenergic neurones, after chronic antidepressant treatment, has demonstrated that integrated mechanisms are operative for the function of the overall system.

Animals↗
PubMed1983

Ethanolamine-O-sulfate enhances gamma-aminobutyric acid secretion into hypophysial portal blood and lowers serum prolactin concentrations.

In ovariectomized rats the intraventricular administration of ethanolamine-O-sulfate (EOS, 300 micrograms), a specific, competitive and catalytic inhibitor of gamma-aminobutyric acid (GABA) transaminase, induced 3-4 h later a marked reduction in serum prolactin (PRL) concentrations and a 3- to 4-fold rise in the concentration of GABA in pituitary stalk, but not systemic, plasma. The administration of EOS also resulted in an elevation of GABA concentrations in the hypothalamus. These results demonstrate that GABA in pituitary stalk plasma is derived from the central nervous system and that an abrupt increase in the concentration of GABA in hypophysial portal blood is associated with a suppression of PRL secretion.

Animals↗
PubMed1982

GABAergic control of anterior pituitary hormone secretion.

Anatomical and biochemical studies have identified a hypothalamic tubero-infundibular GABAergic system, which plays a functional role on anterior pituitary hormone secretion. Experimental and clinical evidence support the presence of a dual component in the action of GABA; one mediated via the central nervous system and the other exerted directly at the anterior pituitary level. The two sites of action may be responsible for the excitatory and inhibitory effects of GABA on pituitary hormone and especially prolactin secretion. The future characterization of this system will provide a better understanding of the involvement of GABA in the physiology of anterior pituitary hormone secretion and will contribute to the development of new pharmacological agents for the therapy of neuroendocrine disorders.

Adrenocorticotropic Hormone↗
PubMed1982

Cerebellar cyclic GMP and behavioral effects after acute and repeated administration of benzodiazepines in mice.

The previous finding that benzodiazepine-induced changes in cyclic GMP in the cerebellum were poorly correlated with the impairment of motor function has now been extended further. The effects following acute, and during repeated administration of diazepam, quazepam and flurazepam were studied in mice. A 10 day period of daily treatment with 5 mg/kg p.o. was used in these studies. The content of cGMP was significantly reduced (P less than 0.05) during the chronic administration of quazepam and flurazepam except after 10 days for flurazepam. After diazepam, cGMP levels were lower than in control animals but a significant difference was observed only at the sixth and tenth day because a minimal threshold dose was used. Antagonism of pentylenetetrazol-induced convulsions was significantly (P less than 0.05) effective over the 10 day treatment for all drugs. Spontaneous motor activity was reduced by quazepam given for two days and by diazepam given for one day while this measure was unaffected by flurazepam given at the same dose which was effective in the other tests. These results further supported a lack of association between changes of cGMP content in the cerebellum and sedative or muscle relaxant effects of benzodiazepines, whereas the lowering of cGMP levels seemed to parallel effects that are not subject to tolerance such as the antagonism of pentylenetetrazol-induced convulsions.

Animals↗
PubMed1982

Glycosaminoglycans in human cerebral tumors. Part II. Histochemical findings and correlations.

The occurrence and the distribution of GAGs have been studied histochemically in 224 human cerebral tumors by means of Alcian blue techniques. In the normal peritumoral gray matter the alcianophilia is stronger than in the white matter and demonstrated the presence of HA and CS. In the glioma group the alcianophilia, due to HA and CS, is mainly related to the presence of infiltrated cortex. In the other tumors, GAGs are histochemically disclosed in relation to collagen, reticulin, mesodermic areas, etc. The vessels of every tumor show a positive staining for HA, CS and HS. The histochemical findings are consistent with the biochemical ones as reported in Part I, even though the significance of GAGs in cerebral tumors remains unknown.

Astrocytoma↗