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Biomedical subjects

G Racagni

Publications and source records attributed to G Racagni.

At least 145 records · Page 8Linked to original sources
PubMed1986

Endocrine modulation of gamma-aminobutyric acidergic innervation in the rat fallopian tube.

The present study investigates the effect of different endocrine manipulations on the gamma-aminobutyric acid (GABA)-ergic system in the rat fallopian tube. Either hypophysectomy or ovariectomy induced a significant decrease of glutamic acid decarboxylase (GAD) activity and of GABA levels in in situ tubes. This effect was completely reversed by either gonadotropins or combined estrogen-progesterone administration, respectively. Estrogen or progesterone alone proved less effective than the administration of both steroids in counteracting the effect of ovariectomy on GAD activity. The in vitro incubation of ovariectomized rat fallopian tubes with estrogen-progesterone for 1 h failed to counteract the reduction of the GAd activity induced by surgical manipulation. The in vivo effect of estrogen-progesterone administration on the GABA-ergic system seems to be specific since steroid treatment induced the synthesis of an enzyme which was immunologically identical to the GAD present in the fallopian tube and brain of normal diestrous rat. Autotransplantation of the fallopian tube under the skin brought about a decrease of GAD activity similar to that obtained after ovariectomy. In this situation, however, estrogen-progesterone administration did not counteract the decrease of GAD activity induced by fallopian tube deafferentation. The present results demonstrate that an interaction between the GABA-ergic system and the hypothalamo-pituitary-gonadal axis seems to be operative at the level of the rat fallopian tube. However, the physiological meaning of this interrelationship between the endocrine and the peripheral nervous systems remains to be clarified.

Animals↗
PubMed1985

Effect of single or repeated estrogen administration on tuberoinfundibular GABA neurons and anterior pituitary GABA receptors: biochemical and functional studies.

The effect of single or protracted administration of estradiol valerate on the hypothalamo-pituitary gamma-aminobutyric acid (GABA)ergic system and on plasma prolactin levels has been evaluated in female rats 2 months after the last (chronic treatment) or the single dose of the steroid. In the group of animals receiving one dose of estrogen, no modifications were detected in the activity of the tuberoinfundibular GABAergic neurons as implied by unchanged GABA accumulation either in the median eminence or the anterior pituitary after blockade of GABA catabolism with ethanolamine-O-sulphate. However, a complete disappearance of the low affinity population of GABA receptors in the anterior pituitary was observed. In this experimental condition, where baseline prolactin levels were 3-fold higher than in control rats, muscimol, a potent GABA agonist, was effective in significantly lowering plasma prolactin concentrations. Chronic estradiol valerate administration reduced GABA accumulation in the median eminence and the anterior pituitary at 4, but not at 2 h, after intracerebroventricular injection of ethanolamine-O-sulphate. Moreover, in this instance, a complete disappearance of the high affinity population of GABA receptors in the anterior pituitary was detected. Long-term estrogen administration induced also a 55-fold increase of plasma prolactin titers and muscimol was ineffective in reducing prolactin concentrations in plasma. The ability of muscimol to inhibit prolactin release only in single-estrogen-treated animals strongly suggests that the high affinity population of anterior pituitary GABA receptors is that involved in the mechanisms whereby GABA inhibits prolactin release from anterior pituitary.

Animals↗
PubMed1985

Studies on the up regulation of alpha-adrenoceptors on rat hippocampal perikarya by chemical lesion of the median raphe nucleus.

Neurotoxin-induced lesion of the serotonergic raphe-hippocampal pathway produced about a 50% increase in the density of a nM affinity alpha-adrenergic binding site for (3H)WB-4101 in rat hippocampus 18 days postlesion without altering the specific binding of (3H)5-HT to serotonergic receptors. The chronic i.c.v. infusion of serotonin by minipump started at the appropriate time averted or reverted the effect. The dynamics of noradrenergic neurotransmission in the hippocampus was not impaired by lesion of the median raphe nucleus as determined by the uptake and turnover of noradrenaline as well as its release - as reflected by the normetanephrine concentration. In addition, neurotoxin-induced lesion of the dorsal noradrenergic bundle failed to alter either the Bmax or the Kd of (3H)WB-4101 binding to the nM site. Kainic acid-induced destruction of perikarya depressed the nM (3H)WB-4101 binding sites by 60% and completely prevented the up regulation caused by lesion of the median raphe nucleus. Thus, the supersensitivity-like response of the adrenoceptors to the lack of serotonin appears to be localized on kainate-sensitive cells within the hippocampus.

Animals↗
PubMed1985

Interaction of SCH 23390, a D-1-selective antagonist, with the anterior pituitary D-2 receptors and prolactin secretion in the rat.

The affinity of the dopamine-1 (D-1) selective antagonist SCH 23390 (SCH) towards the dopamine-2 (D-2) receptor population present in the anterior pituitary (AP) was assessed in vitro and in vivo. [3H]Spiperone binding was used as biochemical marker for D-2 receptors in the rat AP and prolactin (PRL) was determined as a measure of the functional response to AP-D-2 blockade. SCH displayed weak activity in inhibiting [3H]spiperone binding in both AP and striatal membranes. The affinity was similar to that exhibited by sulpiride (mu molar range) but lower than that of haloperidol (HAL) (nmolar range). However inhibition of [3H]spiperone by SCH in the AP occurred in a biphasic manner indicating the existence of two D-2 sites with different affinity for the compound. SCH produced a transient and dose-dependent increase in plasma PRL levels when given by the subcutaneous (s.c.) route. A significant rise of PRL levels was observed only 30 min after the administration of high doses of SCH by the intraperitoneal (i.p.) route. SCH counteracted the inhibiting effect of apomorphine on PRL release and potentiated the stimulation effect of low doses of sulpiride on PRL secretion. The low affinity of SCH towards AP-D-2 receptors could be responsible for the small and short-lived increase in PRL secretion. This effect occurred at doses higher than those active in tests predictive for antipsychotic activity, which may depend directly on interaction with D-1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Biochemical and behavioral changes in rats after prolonged treatment with desipramine: interaction with p-chlorophenylalanine.

The decrease in the Bmax value of 3H-dihydroalprenolol (3H-DHA) binding to cortical membranes of rat brain induced by long-term administration of desipramine (DMI) was prevented by concomitant treatment with parachlorophenylalanine (pCPA). Acute administration of DMI significantly decreased locomotor activity in saline- and (pCPA)-pretreated rats. DMI-induced inhibition of locomotor activity was abolished in (pCPA)-pretreated rats chronically treated with DMI. Conversely, in pCPA-pretreated animals, acute DMI could still significantly decrease the locomotion of chronically DMI-treated rats. The data presented indicate that an intact serotoninergic system is required to enable antidepressant drugs to induce biochemical and behavioral changes following their chronic administration.

Animals↗
PubMed1985

Neurochemical studies on GABAergic and aminergic systems in the rat brain following acute and chronic piracetam administration.

In view of the metabolic and behavioural effects of piracetam (P), a cyclic derivative of gamma-aminobutyric acid (GABA), in experimental animals and in man, it was of interest to investigate the effect of acute or chronic administration of the compound on the function of different brain neurotransmitter systems. P was ineffective in modifying either synthesis release, uptake or post- synaptic binding sites for GABA. Acute P injection decreased dose-dependently cGMP levels in the rat cerebellum. Moreover, this effect was not mediated through a GABAergic mechanism. An acute challenge with Piracetam 15 days after chronic treatment with the compound increased DOPAC levels in the striatum and counteracted haloperidol-induced PRL rise. Furthermore, chronic P administration increased normetanephrine levels in the cerebral cortex, an index of the release of norepinephrine at the synaptic level, and induced a desensitization of beta-adrenoceptors in this same brain area. In conclusion, besides the well documented effect of P on cholinergic neurons, P seems to exert its biological and behavioural effects through activation of catecholaminergic mechanisms.

Animals↗
PubMed1985

Effects of an extract of Ginkgo biloba on noradrenergic systems of rat cerebral cortex.

Oral treatment of rats with Ginkgo biloba extract (Gb) elicited a biphasic effect on normetanephrine (NMN) content of cerebral cortex; an initial decrease was evident after 45 minutes, followed by a marked increase that was evident after 14 days. Chronic treatment with Gb led to decreases in the density of 3H-dihydroalprenolol binding (after 27 days or 2 months) and in isoproterenol-stimulated adenylate cyclase activity (after 2 months) of the cerebral cortex. Taken together, these results indicate that the effects of Gb on the central beta-adrenergic system might be involved in its therapeutic actions.

Adenylyl Cyclases↗
PubMed1985

Presynaptic and transynaptic mechanisms involved in the subsensitivity of rat cortical noradrenergic system after long-term antidepressant treatment.

Chronic treatment with antidepressants has been shown to produce a subsensitivity of noradrenergic neurons, both at presynaptic and postsynaptic sites. Important mechanisms, whereby the activity of noradrenergic neurons is regulated, could be the sensitivity of presynaptic alpha 2-adrenoceptors and the participation of transynaptic mechanisms involving other neurons. In this report we demonstrate that transynaptic factors involving the serotonergic system may be relevant to the regulation of the function of alpha 2-receptors in antidepressant chronically treated animals. In fact, we provide evidence of a markedly deminished responsiveness of noradrenergic neurons to an alpha 2-agonist (clonidine) or antagonist (mianserin) in biochemical and behavioral studies following serotonergic denervation with 5,7-dihydroxytryptamine. These results indicate that a functional interrelationship between serotonergic and noradrenergic systems might play an important role in the adaptive changes which bring the noradrenergic neurons to a lower level of activity after chronic antidepressant administration.

5,7-Dihydroxytryptamine↗
PubMed1985

Prolactin in cerebrospinal fluid increases the synthesis and release of hypothalamic gamma-aminobutyric acid.

The effect of intracerebroventricularly (i.v.t.)-injected rat prolactin (2 micrograms/rat) on the function of tuberoinfundibular gamma-aminobutyric acid (GABA)ergic neurones was assessed in adult male rats by measuring the activity of glutamic acid decarboxylase (GAD) in the mediobasal hypothalamus (MBH) and the concentrations of GABA in hypophysial portal plasma and in the anterior pituitary gland. Fourteen hours after i.v.t. injection of rat prolactin the activity of GAD in the MBH was significantly (P less than 0.05) increased and it remained elevated for at least 16 h after injection. The mean concentrations of GABA in hypophysial portal plasma and in the anterior pituitary were twice those found in vehicle-treated controls 16 h after administration of rat prolactin; no significant effects were observed at earlier time-periods. A significant (P less than 0.01) and long-lasting decrease in endogenous plasma prolactin concentrations was detected 2 h after the i.v.t. injection of rat prolactin and the concentrations remained suppressed for up to 16 h. The present results are consistent with the concept that the activity of tuberoinfundibular GABAergic neurones is regulated, at least in part, by circulating prolactin. The ability of prolactin to accelerate the synthesis and release of GABA in the MBH might constitute a short loop feedback system by which the hormone regulates its own secretion.

Animals↗
PubMed1984

[Markers of brain tumors].

Biological markers of tumors are compounds or enzymatic activities measurable in body fluids. Their presence or concentration must be linked to tumoral growth. The markers of the central nervous system tumors are detected in CSF. Alpha-feto-protein, carcinoembryonic antigen, human chorionic gonadotropin, adenohypophyseal peptide hormones, enzymes, etc., have found some application in the early diagnosis of leptomeningeal metastasis. Other applications involve the early detection and recurrency of primary brain tumors, as well as the evaluation of efficacy of their therapy. The tests based on the CSF content of desmosterol and polyamines have been studied extensively. Their rationale is discussed and specificity, sensitivity, efficiency and predictive value are considered. Experimental results concerning a new possible biochemical marker, based on CSF concentration of cyclic adenosine monophosphate, are reported.

Brain Neoplasms↗
PubMed1984

Modulation of opioid system in C57 mice after repeated treatment with morphine and naloxone: biochemical and behavioral correlates.

C57 BL/6J (C57) mice display a particular pattern of responses following morphine administration, such as a rapid development of tolerance to the pharmacological action of the opiate and an increase in locomotor activity after a single injection of the drug. We have measured met-enkephalin content and the responsiveness of different opiate receptors after repeated administration of morphine and naloxone. Prolonged morphine administration changes neither met-enkephalin levels, nor the density of the opiate receptors in mice brain. In contrast repeated administration of the opiate antagonist naloxone, produced a marked increase in the number of 3H- DHM and 3H- DADLE binding sites in striatum and brainstem without modifying met-enkephalin concentrations. Behavioral studies have indicated that the morphine-induced increase in locomotor activity is enhanced in naloxone pretreated mice, thus suggesting a possible correlation between the behavioral response to morphine in C57 mice and the higher number of opiate receptors in the striatum.

Animals↗
PubMed1984

Behavioural changes in rats after prenatal administration of typical and atypical antidepressants.

Prenatal administration of typical (desipramine, DMI) and atypical (viloxazine, VX and mianserin, MS) antidepressants, at dose levels which do not influence reproductive success or neonatal mortality, produces subtle behavioural changes in offspring of treated rats. Physical signs, such as pinna detachment (unfolding of external ear) and eye opening, were not modified by prenatal exposure to any of the antidepressants tested. However, at 23 days of age, DMI, MS and VX (only in males) pretreated rats showed higher levels of locomotor activity with respect to the control group. At 60 days of age, locomotor activity levels in DMI-exposed animals were still higher than in the saline-pretreated rats.

Aging↗