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Biomedical subjects

F Drago

Publications and source records attributed to F Drago.

At least 163 records · Page 9Linked to original sources

Spatial learning potentiates the stimulation of phosphoinositide hydrolysis by excitatory amino acids in rat hippocampal slices.

Stimulation of phosphoinositide (PI) hydrolysis by excitatory amino acids (glutamate and ibotenate) or norepinephrine was potentiated in hippocampal slices from rats trained in an eight-arm radial maze, used as a test of spatial learning. No difference in basal or carbamylcholine-stimulated PI hydrolysis was found between control and trained animals. An increased PI response to excitatory amino acids and norepinephrine was not found in hippocampal slices prepared from animals trained in a shock conditioning avoidance test. These results suggest a possible involvement of specific glutamate receptors coupled with PI hydrolysis in the synaptic mechanisms underlying formation and/or storage of spatial memory.

Animals↗

Hyperprolactinaemia increases intraocular pressure in humans.

Nine female and 2 male hyperprolactinaemic patients (plasma prolactin levels averaging 180-420 ng/ml) were subjected to measurements of intraocular pressure (IOP) either under basal conditions or after water load in comparison with 5 healthy volunteers. Basal values of IOP in hyperprolactinaemic patients were 37.8% higher than those of controls. Moreover, after water load hyperprolactinaemic patients showed a sustained increase in IOP that reached values of pathological significance. These results suggest that prolactin may contribute to the hormonal regulation of IOP in humans.

Adenoma↗

Desenkephalin-gamma-endorphin restores the impaired sensitivity of hypophysectomized rats to small doses of apomorphine.

Hypophysectomized male rats, tested 7 days after removal of the pituitary, showed a reduced sensitivity to small doses of apomorphine. In these rats, subcutaneous (s.c.) treatment with apomorphine (25, 100 or 250 micrograms/kg) did not elicit any reduction in locomotor activity measured 5 min after injection in contrast to that observed in sham-operated control rats. The enhancement of locomotor activity and stereotyped behavior, 20 min after the s.c. administration of apomorphine, was similar in hypophysectomized rats and in control animals. Prolactin does not seem to be implicated in this altered sensitivity, since hyperprolactinaemia induced by pituitary homografts under the kidney capsule did not change the response to apomorphine in hypophysectomized rats. Chronic treatment with desenkephalin-gamma-endorphin (DE gamma E), a beta-endorphin fragment with neuroleptic-like properties, administered s.c. twice a day for 7 days at the dose of 10 micrograms/rat, restored the sensitivity to small doses of apomorphine in the hypophysectomized rats. The data suggest that removal of the pituitary leads to impaired sensitivity of presumably presynaptically located dopamine receptors mediating the effects of small doses of apomorphine without altering the sensitivity of postsynaptically located dopamine receptors that mediate the hypermotility and stereotypy induced by apomorphine. This impaired sensitivity to low doses of apomorphine could be restored by DE gamma E but not by prolactin, supporting the conclusions from previous experiments that DE gamma E and prolactin may selectively interfere with pre- and postsynaptic dopamine receptors respectively.

Animals↗

Oxytocin potently enhances novelty-induced grooming behavior in the rat.

Intracerebroventricular (i.c.v.) injection of oxytocin was followed by an enhancement of novelty-induced grooming in male and female rats. This effect was dose-dependent, in a dose range of 0.1-10 micrograms. Grooming activity of rats injected i.c.v. with 10 micrograms of oxytocin was 9-fold higher than that of saline-injected controls. The analysis of behavioral element composition revealed an increased occurrence of genital grooming in oxytocin-injected rats. A time-course study revealed a sustained increase in grooming activity of oxytocin-treated rats during 45 min of behavioral testing. Intraperitoneal (i.p.) injection of the dopamine antagonist, haloperidol, totally suppressed oxytocin-enhanced grooming. Furthermore, i.p. injection of the opiate receptor antagonist, naloxone, was followed by an attenuation but not a suppression of grooming enhanced by i.c.v. administration of oxytocin. In addition, a small but significant increase in grooming activity was observed after subcutaneous injection of oxytocin. These results suggest that oxytocin-enhanced grooming behavior involves central mechanisms, e.g. dopamine and opioid transmission in the brain.

Animals↗

Hyperprolactinaemia alleviates behavioral alterations of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

Male rats homozygous for hereditary hypothalamic diabetes insipidus (HO) and their heterozygous (HE) and normal (NO) variants (Brattleboro rats) were made hyperprolactinaemic by homografting two adenopituitaries under the kidney capsule. The high water intake and urine output of homozygous diabetic sham-operated rats (sham-HO) were similar to those of homografted HO animals. Also, hyperprolactinaemia failed to change the water intake and urine output of HE and NO rats, as compared to those of heterozygous (sham-HE) and normal (sham-NO) sham-operated animals. Compared to sham-HE and sham-NO animals, sham-HO rats showed a slow acquisition of active avoidance responses, a facilitated extinction of a pole jumping avoidance behavior and a reduced retention of a passive avoidance response. However, an improved performance of acquisition and retention behaviors up to the level of sham-HEs and sham-NOs was observed in homografted HO rats. Hyperprolactinaemia resulted in a reduced responsiveness to electrical footshock in HO, HE and NO animals, and in facilitated acquisition of active avoidance responses in HE and NO rats, but it failed to affect avoidance extinction and retention in the latter variants. These results suggest that the behavioral alterations shown by homozygous diabetes insipidus rats are alleviated by hyperprolactinaemia although high levels of plasma prolactin do not interfere with the mechanisms regulating water intake and urine output. In addition, hyperprolactinaemia affects the behavior of heterozygous and normal variants of Brattleboro strain but in a selective way.

Animals↗

Dopamine neurotransmission in the nucleus accumbens may be involved in oxytocin-enhanced grooming behavior of the rat.

Intracerebroventricular (ICV) infusion of a low dose of oxytocin enhanced novelty-induced grooming in male rats. The present experiments were undertaken to investigate whether dopamine neurotransmission in the nucleus accumbens is involved in this effect. Bilateral lesions of the nucleus accumbens by microinjections of 6-hydroxydopamine (6-OHDA) totally prevented the enhancement of grooming behavior after subsequent ICV infusion of oxytocin. Furthermore, bilateral injections of the dopamine receptor antagonist, haloperidol, into the nucleus accumbens completely suppressed grooming behavior of rats infused ICV with oxytocin. These results suggest that dopamine neurotransmission in the nucleus accumbens is involved in the behavioral response enhanced by the peptide.

Animals↗

Behavioral effects of acetyl-l-carnitine in the male rat.

The behavioral activity of carnitine acetylate derivative, acetyl-l-carnitine has been studied in the male rat. Intraperitoneal (IP) injection of acetyl-l-carnitine was followed by an increase in ambulation and rearing items in the open field behavior. Both the number of conditioned avoidance response (CARs) and the percentage of learners in the acquisition of shuttle-box active avoidance behavior appeared to be increased by IP or intracerebroventricular (ICV) injection of the drug at different doses. Subchronic administration of the drug mimicked the effects found after acute injection. The number of CARs in the extinction of shuttle-box active avoidance behavior appeared to be increased after acute IP or ICV injection, and after subchronic administration of acetyl-l-carnitine. The retention of passive avoidance behavior was facilitated by IP injection of the substance. The behavioral effects of acetyl-l-carnitine may involve central mechanisms, e.g., cholinergic neurotransmission in the brain.

Acetylcarnitine↗

Effect of dopamine agonists and antagonists on neurotensin-induced antinociception.

In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.

Analgesics↗

A comparison of grooming behavior potencies of neurohypophyseal nonapeptides.

We have previously demonstrated that intracerebroventricular (ICV) administration of oxytocin (OXY) enhanced grooming behaviors in male and female rats at a 1 microgram dose. In the present study female rats were injected ICV with 1 microgram OXY or equimolar doses of other peptides. At this dose arginine-vasopressin (AVP), arginine-vasotocin (AVT) and lysine-vasopressin (LVP), as well as alpha-MSH, were as effective as OXY in increasing grooming behavior. At equimolar doses, ACTH1-10, tocinoic acid (the ring structure of OXY) and Pro-Leu-Gly-NH2 (the tail structure of OXY) had no significant effect on grooming behavior. The potency of AVP and AVT was determined across a 0.05-5 microgram dose range. Grooming scores increased in an apparent linear manner across a similar OXY dose range. Both AVP and AVT, however, manifested an inverted U grooming response curve. Maximum grooming scores resulted from a 0.1 microgram dose of AVT or a 0.5 microgram AVP dose. Analyses of the aspects of grooming separately found that nonapeptides OXY, AVP and AVT all elevated body grooming, washing, and scratching. Because AVT and AVP administration resulted in grooming scores significantly higher than OXY at lower doses, we concluded that the CNS is more sensitive to the effects of AVT and AVP on grooming behavior than OXY.

Adrenocorticotropic Hormone↗

Intracerebroventricular injection of anti-prolactin serum suppresses excessive grooming of pituitary homografted rats.

Rats with endogenous hyperprolactinaemia, as induced by pituitary homografts under the kidney capsule, displayed increased grooming behavior as compared to that of sham-operated animals. Twelve days after surgery, intracerebroventricular injection of anti-prolactin serum (dilution 1:100, 1 microliter) suppressed the excessive grooming of homografted rats. These observations suggest that prolactin from a peripheral source may reach the central nervous system to affect brain mechanisms involved in grooming behavior.

Adrenocorticotropic Hormone↗

Effect of sulpiride on chronic abstinence syndrome in addicted patients.

A total of 410 patients (342 men and 68 women) addicted to heroin for at least 38 months, with or without previous methadone treatment experience, were treated with sulpiride before the appearance of withdrawal syndrome. The drug was injected intramuscularly in a single administration at a dosage of 600 mg. Successively, sulpiride was injected intramuscularly at a dosage of 200 mg 3 times per day from days 2-21 of hospitalization, and then at a dosage of 100 and 50 mg 3 times per day (days 22-25 and 26-29, respectively). All patients showed a suppression of withdrawal signs and symptoms within 6 days of treatment, as assessed by subjective and objective scores. The effect of sulpiride was compared with that of placebo administered to a control group of 10 heroin addicts. Because prolactin has been shown to reduce the dependence of rats to heroin and the naloxone-precipitated withdrawal syndrome in morphine-addicted animals, the effects of sulpiride on heroin addiction may be related to the hyperprolactinemic action of this drug.

Adolescent↗

Neuropeptide therapies in chronic schizophrenia: TRH and vasopressin administration.

Twenty-three chronic undifferentiated schizophrenics, 13 women and 10 men, aged 37-64 years with 15-to 40-year histories of the disease were given either thyrotropin-releasing hormone (TRH) (10 subjects) or DDAVP (13 subjects) with the aim to improve the negative symptoms of the disease and memory. TRH (600 micrograms i.v.) and DDAVP (4 micrograms i.m.) were administered every other day for 30 days. Negative symptoms were monitored by the Andreasen rating scale and by the Honingfeld NOSIE rating scale, memory by the Folstein 'Mini mental State' rating scale and by the Luria-Nebraska rating scale before therapy and then at days 15, 16, 30 and 31 of treatment. Both therapies significantly improved negative symptoms. Memory was significantly improved in all the patients treated with TRH and in 9 of the 13 patients treated with DDAVP, who presented less severe cognitive impairments. A peripheral mechanism of action of DDAVP was excluded by the observation that plasma electrolytes and osmolality, blood pressure, ECG patterns, 24-hour urine volume and specific gravity, basal plasma cortisol and growth hormone levels and weight of the patients were unchanged during therapy. TRH treatment induced a transient borderline hyperthyroidism at day 15 and a progressive decrease of the thyrotropin response to TRH stimulation. A common mechanism of action of the two peptides on the central noradrenergic system is suggested.

Adult↗

Hormonal modulation of central dopaminergic transmission.

Central dopaminergic transmission is subjected to influences of various hormones of hypophyseal and extra-hypophyseal origin. Ablation of hypophysis prevents the supersensitivity of central dopamine receptors induced by chronic treatment with the dopamine receptor antagonist, haloperidol. Furthermore, hypophysectomized rats show a potentiation of hypomotility induced by low doses of the dopamine receptor agonist, apomorphine. Among the hypophyseal hormones, prolactin (PRL) seems to exert a modulatory activity on central dopamine transmission. Exogenous administration of PRL increases the density of dopamine receptors in intact and hypophysectomized rats. Furthermore, hyperprolactinaemic rats show alterations of the concentration and turnover of dopamine in various brain areas, and a potentiation of apomorphine-induced stereotypies. Endorphins related to gamma-endorphin also modulate central dopamine transmission. In particular, des-enkephalin-gamma-endorphin seems to interfere specifically with apomorphine-sensitive dopamine receptors. The administration of this endorphin is followed by a potentiation of hypomotility induced by low doses of apomorphine, and restores the sensitivity of hypophysectomized rats to these doses. The administration of estrogens also influences the sensitivity of central dopamine receptors. Depending on the doses, these hormones can potentiate or inhibit the dopaminergic neurotransmission in the brain.

Animals↗

[Monitoring cardiac rhythm after the Mustard intervention for transposition of the great arteries].

Before Mustard's operation 27 children, from 2 days to 11 months old, with simple or complex transposition of the great vessels, underwent an electrocardiogram at rest. After operation, all the children underwent a standard electrocardiogram and 24 hours continuous Holter monitoring. Successive electrocardiograms at rest were recorded in all patients, and eleven children were successfully examined by dynamic electrocardiogram. The electrocardiogram at rest showed a sinusal rhythm in 66.7 of the patients; during the follow-up, in 33.3% non sinusal rhythm was recorded. The continuous 24 hours dynamic electrocardiogram, immediately after surgery, revealed 25.9% of the patients with non-sinusal rhythm. After 7 months, the Holter monitoring showed, in one case, a severe sinus node disfunction. Our data and those of the literature confirm the importance to follow these patients during a long period of time, because it was found that, even bedately, can develop serious arrhythmias.

Electrocardiography↗

Somatic growth in hypophysectomized pituitary-homografted rats is promoted by prolactin.

Hypophysectomized male rats bearing a homograft of two adenopituitaries under the kidney capsule showed a significant increase in b.wt as compared to hypophysectomized non-homografted animals. Radioimmunoassay of growth hormone (GH), ACTH, alpha-MSH, beta-endorphin and prolactin (PRL) revealed that only the latter was highly increased in the plasma of hypophysectomized homografted rats. These animals showed also increased levels of plasma corticosterone. However, daily injection of corticosterone failed to promote somatic growth in hypophysectomized non-homografted rats. These results suggest that PRL, and not other hormonal factors, promotes somatic growth in hypophysectomized homografted rats, and stress the concept that only PRL is secreted in significant amounts by pituitary homografts.

Animals↗