Biomedical subjects

W Fratta

Publications and source records attributed to W Fratta.

At least 19 recordsLinked to original sources

PubMed1992

Calcium antagonists isradipine and nimodipine suppress cocaine and morphine intravenous self-administration in drug-naive mice.

The effect of isradipine and nimodipine, two dihydropyridine calcium antagonists, on intravenous self-administration of cocaine and morphine in naive mice has been investigated. When morphine or cocaine injections were made contingent upon nose-poke response by naive mice, they increased their rate of nose-poking with respect to animals receiving contingent saline injections or yoked control animals, receiving noncontingent cocaine or morphine injections. Pretreatment of mice with isradipine (1.0-3.0 mg/kg, SC) or nimodipine (5-20 mg/kg, SC) inhibited in a dose-related manner self-administration both of cocaine and morphine contingent upon a nose-poke response. The ED50 of isradipine against cocaine and morphine self-administration was 1.7 and 2.1 mg/kg, respectively. The relative values for nimodipine were 14.5 and 11.4 mg/kg, respectively. These data suggest that nimodipine and, especially, isradipine suppress the reinforcing properties of morphine and cocaine and may be an effective pharmacotherapy for treatment of cocaine and heroin abuse.

Animals↗

PubMed1992

Dopamine D1 and opioid receptor binding changes in the limbic system of sleep deprived rats.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was potently antagonized by the administration of the D1 selective antagonist SCH 23390 and by the opioid antagonist naloxone. In this paper we show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain area. These data suggest an active role of limbic dopamine and opioid systems in the generation of arousal and insomnia related to sleep deprivation-induced stress.

Animals↗

PubMed1991

Sleep deprivation decreases mu and delta opioid receptor binding in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was antagonized by the administration of the opioid receptor antagonist naloxone and increased by opioid agonists. In this paper we show that concomitantly with this behavior, a decreased Bmax of mu and delta opioid receptors is present in the limbic system of these animals. These data suggest an active role of limbic mu and delta receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.

Animals↗

PubMed1991

The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine.

The effect of a dihydropyridine (DHP) calcium antagonist, PN 200-110, on cocaine reinforcing properties was investigated using conditioned place preference paradigm. PN 200-110 in nonsedative doses (0.62-1.25-2.5 mg/kg SC) was able to inhibit cocaine-(10 mg/kg IP) induced place preference with ED50 1.57 (0.88-2.58). The results suggest a possible use of DHPs in the treatment of cocaine-related disorders.

Animals↗

PubMed1990

Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rats displayed particular behaviour characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behaviour was potently antagonized by the administration of the D1-selective antagonist SCH 23390. In this paper we show that concomitantly to this behaviour, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. These data suggest an active role of limbic D1 receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.

Adenylyl Cyclases↗

PubMed1990

Corticotropin-releasing factor (CRF) increases paradoxical sleep (PS) rebound in PS-deprived rats.

The intracerebroventricular injection (1 microgram) of murine corticotropin-releasing factor (r-CRF) to rats after 72 h of sleep deprivation markedly postponed the sleep onset, reduced slow wave sleep and prolonged the duration of paradoxical sleep (PS) episodes. Moreover, CRF is-to our knowledge-the first compound to be able to further prolong PS in a condition (sleep deprivation) in which its duration is already increased. Our findings raise the possibility that CRF might play a physiological role in the regulation of the sleep-wakefulness cycle.

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

Possible mechanism of antidepressant effect of L-sulpiride.

L-Sulpiride is a dopamine (DA)-receptor blocker that acts as an antidepressant at low doses. We have reviewed evidence suggesting that the antidepressant effect of L-sulpiride may depend on the activation of DA transmission secondary to the blockade of DA autoreceptors.

Depressive Disorder↗

PubMed1990

Plasma alpha-melanocyte-stimulating hormone during the menstrual cycle in women.

alpha-Melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) immunoreactivity (IR) was measured in the blood of 22 healthy women with normal ovulatory process in the early and late follicular (near to ovulation) phases and in the early luteal phase of the menstrual cycle. Plasma alpha-MSH IR ranged from undetectable values to 81.3 pg/ml, the highest levels being found in the late follicular phase (15.52 +/- 4.16 pg/ml). In contrast, plasma ACTH IR was always detectable (range: 18.5-63.2 pg/ml), but its concentration did not differ significantly between the 3 phases of the menstrual cycle. High-pressure liquid chromatography fractionation of Sep pak C18-purified alpha-MSH IR revealed in all 3 phases the presence of 3 major peaks of alpha-MSH IR, coeluting with desacetyl-alpha-MSH, alpha-MSH and diacetyl-alpha-MSH, respectively. The most abundant peak always coeluted with authentic desacetyl-alpha-MSH, and the ratio between this deacetylated and the other 2 acetylated forms was similar in the 2 follicular phases (1:1.25 and 1:1.16 in the early and late phase, respectively), but significantly different in the luteal phase (1:0.48). The fluctuations in plasma concentration of the above MSH-related peptides suggest that different rates of alpha-MSH acetylation and release take place in the pituitary gland depending on the phase of the menstrual cycle.

Adolescent↗

PubMed1990

Correlation between amniotic levels of alpha-MSH, ACTH and beta-endorphin in late gestation and labour in normal and complicated pregnancies.

alpha-MSH, ACTH and beta-endorphin were measured by radioimmunoassay in samples of amniotic fluid collected from the 32nd to the 38th gestational week and at labour from normal pregnancies and pregnancies complicated by gestosis. In normal pregnancies, the concentration of alpha-MSH, ACTH and beta-endorphin remained relatively constant during the last 7 gestational weeks, but increased at labour above the values of the 38th week by 88, 143 and 96%, respectively. A positive correlation between beta-endorphin and alpha-MSH (r = 0.92) or ACTH (r = 0.76) levels was found when labour values were considered in the regression analysis. In contrast, when labour values were excluded, only a poor positive correlation between beta-endorphin and alpha-MSH (r = 0.52) was found. In complicated pregnancies, alpha-MSH and ACTH concentrations were similar to those found in normal pregnancies: on the other hand, the level of beta-endorphin, was found to be 130% higher than normal. As in normal pregnancies, alpha-MSH, ACTH and beta-endorphin levels increased at labour, but only by 46, 44 and 23%, respectively. In contrast to in normal pregnancies, the correlation between beta-endorphin and alpha-MSH or ACTH was not significantly modified by labour values. The present results confirm and extend previous studies showing that beta-endorphin may be considered a marker of fetal distress and that the fetal pituitary is capable of reacting to stressful stimuli in normal and suffering fetuses.

Adolescent↗

PubMed1988

Des-acetyl-alpha-MSH and not alpha-MSH is the major form of alpha-MSH in amniotic fluid.

Immunoreactive alpha-melanocyte stimulating hormone (IR-alpha-MSH)-like activity was measured by radioimmunoassay (RIA) in at term pregnancy amniotic fluid prior and after adsorption on a Sep-pak C18 cartridge. alpha-MSH activity was 3-4 times lower after Sep-pak purification but, unlike the levels of IR-alpha-MSH in the fluid analyzed in toto, increased linearly with the volume of fluid analyzed. Furthermore, fractionation by high pressure liquid chromatography (HPLC) revealed that IR-alpha-MSH recovered from the Sep-pak was due to several peptides rather than to a single peptide. The most abundant of them (50% of total activity) behaved like authentic des-acetyl-alpha-MSH. Since des-acetyl-alpha-MSH is also the most abundant alpha-MSH-like peptide in the fetal pituitary gland, the present results suggest that the fetal pituitary is a main source of des-acetyl-alpha-MSH in the amniotic fluid.

Amniotic Fluid↗

PubMed1987

Stress-induced insomnia: opioid-dopamine interactions.

REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1987

Different epileptogenic activities of murine and ovine corticotropin-releasing factor.

The behavioral and EEG effects of rat and ovine corticotropin releasing factor (r- and o-CRF) were compared. Both peptides were injected intracerebroventricularly into rats through chronically implanted cannulae. At the doses of 0.1 and 1 microgram both peptides activated the EEG and stimulated motor activity. At the dose of 10 micrograms they produced spiking activity. However, while o-CRF-induced spiking activity was present both in the hippocampus and in the cortical leads and was associated with generalized myoclonic movements, that induced by r-CRF was confined in the hippocampus and was not accompanied by myoclonic movements. Spiking activity induced by r-CRF was suppressed by verapamil, but was not influenced by naloxone.

Animals↗

PubMed1987

Hypophysectomy prevents ACTH-induced yawning and penile erection in rats.

The intracerebroventricular administration of ACTH1-24 (3-5 micrograms/rat) produced a behavioural syndrome characterized by recurrent episodes of penile erection and yawning in rats. Hypophysectomy prevented ACTH1-24-induced yawning and penile erection. These results suggest that pituitary has a "trophic" action not only on peripheral target organs but also on structures in brain controlling specific behavioural responses.

Adrenocorticotropic Hormone↗

PubMed1987

Monosodium glutamate does not alter ACTH- or apomorphine-induced penile erection and yawning.

The effect of the intracerebroventricular (ICV) injection of ACTH 1-24 (1, 5 and 10 micrograms) or the subcutaneous administration of apomorphine (20 and 80 micrograms/kg SC) on spontaneous penile erection and yawning was studied in rats treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic ACTH, alpha-MSH and endorphin-like peptides. Neonatal MSG treatment failed to antagonize either apomorphine- or ACTH-induced yawning in male and female rats, or to alter the number of penile erection episodes induced by the two substances in male rats. In contrast, hypophysectomy, that does not alter the concentration of hypothalamic ACTH and alpha-MSH, caused a marked prevention of apomorphine- and ACTH-induced responses, in agreement with previous studies. The results suggest that the integrity of opiomelanotropinergic neurons in the hypothalamus is not necessary for the induction of yawning and penile erection by ACTH-derived peptides, and that apomorphine and other dopamine agonists apparently do not induce penile erection and yawning by releasing an ACTH-derived peptide in brain.

Adrenocorticotropic Hormone↗

PubMed1985

Biochemical and immunohistochemical evidence for the presence of motilin in pig cerebellum.

The presence of motilin in rat and porcine cerebellum was investigated by using high performance liquid chromatography (HPLC) coupled with radioimmunoassay or immunohistochemistry. The antibodies used for this study were raised against synthetic gastrointestinal porcine motilin, which is, so far, the only known sequence of this peptide. The results obtained show the presence of a sharp peak of motilin-like immunoreactivity after HPLC of porcine cerebellum extracts, with an elution time corresponding to that of synthetic porcine motilin. Motilin-like immunoreactivity was also detected immunohistochemically in porcine cerebellum. However no motilin-like immunoreactivity was detected in rat cerebellum biochemically or immunohistochemically. This finding suggests that if a motilin-like neuropeptide is present in rat cerebellum, its molecular form differs from that present in porcine cerebellum.

Animals↗

PubMed1985

Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine.

Two peptides that crossreact with an antiserum raised against Phe-Met-Arg-Phe-NH2 were purified from bovine brain extract. Their structures were determined to be Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe- NH2 and Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2. The sequences were determined by gas-phase sequencing, except for the COOH-terminal phenylalaninamides. These were assigned on the basis of the reactivity of the peptides with the anti-Phe-Met-Arg-Phe-NH2 antiserum, which appears to recognize the determinant -Arg-Phe-NH2. Both peptides were synthesized, and the synthetic peptides were found to have the same HPLC retention times as the endogenous Phe-Met-Arg-Phe-NH2-immunoreactive peptides, thus confirming the assignment of phenylalaninamide to the COOH-terminal positions. Both of the synthetic peptides were found to decrease tail-flick latency in rats, and the octapeptide was more active than the octadecapeptide. The octapeptide was found also to attenuate the prolongation of the tail-flick latency induced by morphine.

Amino Acid Sequence↗

PubMed1984

Stimulation of dopamine autoreceptors elicits "premature ejaculation" in rats.

Following treatment with dopamine (DA) receptor agonists, such as apomorphine, N-n-propyl-norapomorphine, lisuride and 3-(3-hydroxyphenyl)-N-n-propyl-piperidine (3-PPP) (50, 2.5, 400 and 5000 micrograms/kg, respectively), male rats attain ejaculation with receptive females sooner and after fewer penile intromissions than controls. Since doses of DA agonists needed to produce "premature ejaculation" are within the low dose range needed to stimulate DA autoreceptors, it is suggested that "premature ejaculation" in rats results from inhibition of DA neurotransmission. This hypothesis is supported by the finding that 6 hr after haloperidol (1 mg/kg), rats achieve ejaculation after fewer intromissions than normal.

Animals↗