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Biomedical subjects

G Gessa

Publications and source records attributed to G Gessa.

17 recordsLinked to original sources
PubMed1998

Interaction between menstrual cyclicity and gonadotropin pulsatility.

Pulsatile gonadotropin secretion is a critical endocrine component of the regulation of the normal menstrual cycle. Pulsatile luteinizing hormone (LH) secretion changes dynamically across the menstrual cycle. Derangements of pulsatile LH secretion are found in virtually every menstrual disorder. This article summarizes the key features of pulsatile LH secretion in the normal menstrual cycle and in ovulatory disorders.

Female↗
PubMed1997

Rat tyrosine hydroxylase gene polymorphisms.

The rat tyrosine hydroxylase gene (TH) from a panel of outbred and inbred rat strains has been analysed by Southern blotting, restriction-endonuclease mapping and direct sequencing of PCR-amplified products for detecting DNA polymorphisms. Five polymorphic sites have been characterized. This information may be used in pharmacogenetic studies to determine the influence of the TH gene in animal models of affective disorders and addictive behaviours.

Animals↗
PubMed1997

Effects of acute, chronic ethanol and withdrawal on dorsal raphe neurons: electrophysiological studies.

The effect of a single intravenous administration of ethanol (0.25-1.0 g/kg) on the spontaneous activity of putative serotonin neurons of the dorsal raphe nucleus was studied in unanesthetized rats. Ethanol produced a slight but progressive decline in neuronal activity in 67% (six of nine) of all neurons tested. The remaining 33% (three of nine) were unresponsive. Upon withdrawal of chronic ethanol treatment (1-5 g/kg every 6 h for six consecutive days, 12 h from last ethanol administration), the mean firine rate of dorsal raphe neurons was found to be significantly reduced, by about 30% (n=71), as compared with the control group (n=83), whereas the cells/track index was unaltered. Under these conditions, ethanol administration further reduced firing rate in 67% (four of six) of all the neurons tested. In the remaining 33% (two of six), no response was observed. At 72 h after the last ethanol administration, the mean firing rate of dorsal raphe neurons was found to be within control values (n=90). Further, to evaluate the functional status of the autoreceptors under control conditions and after withdrawal from chronic ethanol, the selective serotonin-1A receptor agonist 8-hydroxy-(2-di-n-propylamino)tetralin was administered intravenously in cumulative doses (1-16 microg/kg) and dose-response curves were generated for both groups. Autoreceptor sensitivity of dorsal raphe neurons was found to be not statistically different in control and ethanol withdrawn rats (n=6 for both groups) as indexed by a similar potency displayed by 8-hydroxy-(2-di-n-propylamino)tetralin in reducing the spontaneous activity of dorsal raphe neurons. The results indicate that, in spite of the widespread use of serotonin transmission potentiating agents in the treatment of alcoholism, neither acute nor withdrawal from chronic ethanol administration produces drastic effects on dorsal raphe neurons. However, the inhibition of dorsal raphe neuronal activity after acute ethanol may be due to the reported ability of ethanol to increase serotonin release from terminal areas. This increased serotonin tone could, at the level of recurrent axon collaterals in the dorsal raphe nucleus, reduce the spontaneous activity of the cells. On the other hand, a similar reduction in spontaneous activity after withdrawal from ethanol correlates well with the reduction in serotonin levels observed under these conditions in microdialysis studies.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence.

Rats chronically administered with ethanol every six hours for six consecutive days show, upon suspension of treatment, a marked somatic withdrawal syndrome characterized by classical neurological signs. The emergence of the behavioral syndrome coincides with a profound decline of dopaminergic mesolimbic neuronal activity which corresponds to a reduction of dopamine outflow in the nucleus accumbens [Diana et al. (1993) Proc. natn. Acad. Sci. U.S.A. 90, 7966-7969]. However, while the behavioral manifestation of the ethanol withdrawal syndrome recedes in about 48 h, electrophysiological indices of mesolimbic dopaminergic function are still reduced 72 h after ethanol discontinuation, thus outlasting the physical signs of ethanol withdrawal syndrome. Dopaminergic neuronal activity is reintegrated by anti-craving drugs such as ethanol itself and gamma-hydroxybutyric acid. It is postulated that the reduced spontaneous activity of mesolimbic dopaminergic neurons may form the neural basis of the dysphoric state which accompanies abrupt interruption of chronic ethanol administration. Pharmacological manipulations of dopaminergic activity targeted at restoring "normal" dopaminergic function after ethanol withdrawal may lead to way to the experimental basis of new therapeutic strategies of alcoholism.

Animals↗
PubMed1995

Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats.

The spontaneous neuronal activity of meso-accumbens dopaminergic neurons was recorded in unanesthetized rats withdrawn from chronic morphine administration (15 days) by means of single cell extracellular recording techniques coupled with antidromic identification from the nucleus accumbens. Twenty-four h after last morphine administration, firing rate and burst firing were found to be drastically reduced and the relative refractory periods of the same neurons were prolonged in morphine-dependent rats as compared with chronic saline-treated controls. The number of spontaneously active dopaminergic neurons, however, did not differ between the two groups. Administration of morphine restored electrophysiological parameters. When rats were tested 2 h after last morphine administration, i.v. challenge with the opiate antagonist naloxone caused an abrupt and virtually complete reduction of dopaminergic firing rate, burst rate and a prolongation of the relative refractory period. These effects were not observed in control rats. The results indicate that the mesolimbic dopaminergic system is tonically reduced in its activity during morphine withdrawal syndrome and considering its role in the reinforcing properties of opioids, its depressed activity during the morphine withdrawal syndrome may bear relevance for the dysphoric state associated to morphine withdrawal in humans.

Animals↗
PubMed1993

Heterogeneous responses of substantia nigra pars reticulata neurons to gamma-hydroxybutyric acid administration.

The effect of intravenous administration of gamma-hydroxybutyric acid (GHB) (50-400 mg/kg) on the firing rate of substantia nigra pars reticulata (SN-PR) neurons was studied by making single cell extracellular recordings in unanesthetized rats. For comparison, the effect of intravenous muscimol (0.5-2 mg/kg) and ethanol (0.5-2 g/kg) was also studied. GHB produced variable effects: dose-related inhibition in 7 out of 18 (38.8%) neurons and no significant change in 11 out of 18 (61.2%) neurons tested. In contrast, muscimol and ethanol produced a dose-related inhibition of the SN-PR firing rate. The results indicate that GHB, unlike muscimol and ethanol, has no profound effect on the activity of SN-PR neurons, and thus disinhibition of dopaminergic units, through inhibition of SN-PR neurons, is probably not the mechanism by which GHB stimulates the firing rate of dopaminergic neurons.

Animals↗
PubMed1993

Potent, extra-channel influence of several calcium-channel modulators on striatal binding of [3H]tyramine.

A number of Ca(2+)-, K(+)-, and Na(+)-channel modulators has been tested with respect to their effects on [3H]tyramine (TY) binding, as a putative marker for the vesicular dopamine (DA) transporter in striatal membrane preparations containing vesicle ghosts. Among organic Ca(2+)-channel modulators, the diphenylalkylamines tested consistently inhibited TY binding: the order of potency was prenylamine > lidoflazine > flunarizine > cinnarizine, with Ki values of 0.1, 0.2, 0.5 and 1.2 microM, respectively. Low (up to 100 nM) concentrations of prenylamine did competitively inhibit TY binding, and higher concentrations provoked a mixed-type inhibition. Furthermore, LIGAND-analysis of competition curves revealed a high- and a low-affinity binding site for prenylamine and flunarizine. The TY binding process was also sensitive to selected K(+)- and Na(+)-channel modulators. Since several Ca(2+)-antagonists are known to affect H(+)-ATPase and the bioenergetics of catecholamine storage vesicles in chromaffin granules, thus affecting monoamine storage, the energy requirements for the formation of the TY/carrier complex were here assessed, assuming similarity between chromaffin granules and synaptic vesicles. TY binding, though not reflecting endovesicle-sequestered TY, was indeed strongly sensitive (with Ki coefficients in the fM or low nM range) to the dissipation of the vesicular transmembrane proton concentration (delta pH), electrical (delta psi), and proton electrochemical (delta microH+) gradients, provoked by a number of specifically targeted agents. It is concluded that Ca(2+)-channel agents of the diphenylalkylamine group may directly affect striatal TY binding due to an extrachannel-regulated competition with TY for the vesicular carrier of DA, as well indirectly, by disruption of the transmembrane energization of the reserpine-sensitive carrier.

Animals↗
PubMed1993

Rewarding and aversive effects of ethanol: interplay of GABA, glutamate and dopamine.

Ethanol (EtOH) administration is considered to elicit its reinforcing properties by stimulating dopaminergic (DA) transmission in the mesolimbic system. Accordingly, (EtOH) activates dopamine neuronal firing in the Ventro-Tegmental Area (VTA) and DA output in the nucleus accumbens. Concomitantly, EtOH reduces the firing rate of Pars Reticulata (PR) neurons which are thought to exert an inhibitory control over DA neurons. Further, chronic ingestion of EtOH produces tolerance to its sedative effects as to the depressant effect on PR neurons but no tolerance to the DA stimulating action. Moreover the NMDA antagonist MK-801, but not SL-820715, stimulates DA firing, suggesting that this effect is not a general characteristic of NMDA receptor antagonists and questioning the possibility that NMDA-receptor blockade may underlie EtOh-induced activation of DA-ergic transmission. The results indicate that activation of the mesolimbic DA tract is essential in the rewarding properties of EtOH and that neither GABA-ergic inhibition nor NMDA-receptor blockade by EtOH, are causally linked to the EtOH-induced activation of DA-ergic transmission.

Alcoholism↗
PubMed1992

Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats.

The electrophysiological activity of mesoaccumbens dopaminergic neurons was monitored during the ethanol-withdrawal syndrome in ethanol-dependent and in control rats. Spontaneous firing was reduced by about half in ethanol-dependent rats as compared to controls. Likewise, the number of spikes/burst was also reduced in ethanol-dependent rats. These results are consistent with the reduction in dopamine release observed during ethanol-withdrawal syndrome and may provide the basis for the aversive effects of the ethanol-withdrawal syndrome.

Animals↗
PubMed1991

Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats.

In unanesthetized rats the intravenous (i.v.) administration of gamma-hydroxybutyric acid (GHB) at the doses of 50-400 mg/kg produced a dose-related stimulation (10-56%) of the firing rate of dopaminergic (DA) neurons in the pars compacta of the substantia nigra. Doses of 1000 and 1500 mg/kg inhibited the firing rate almost completely. In unanesthetized rats the intraperitoneal injection of GHB at the dose of 750 mg/kg produced a brief initial stimulation (23%) followed by a modest reduction in the firing rate (29%). On the other hand, in chloral hydrate-anesthetized rats the i.v. administration of GHB at cumulative doses of up to 200 mg/kg failed to modify the firing rate of DA neurons, while a cumulative dose of 400 mg/kg suppressed neuronal firing. The results indicate that sub-anesthetic doses of GHB stimulate the firing rate of DA neurons in unanesthetized rats.

Anesthesia, General↗
PubMed1989

[3H]tyramine binding: a comparison with neuronal [3H]dopamine uptake and [3H]mazindol binding processes.

[3H]Spiperone [( 3H]SPI) binding sites in rat or bovine striata have been solubilized using CHAPS or digitonin detergents. Solubilized sites retained the binding characteristics of those in native membrane preparations. The same solubilized material, however, did not bind [3H]tyramine [( 3H]PTA), thus indicating that [3H]PTA binding sites and DA receptors are different chemico-physical entities. In membrane preparations or crude synaptosomes obtained from the c.striatum of neonatally-rendered hypothyroid rats, when central DA-pathways are impaired, both [3H]PTA binding and [3H]DA uptake processes were markedly decreased, with no effect on [3H]mazindol [( 3H]MAZ) binding, compared to euthyroids. Reserpine, a well-known inhibitor of DA-uptake into a variety of secretory vesicles, and a potent in vivo and in vitro inhibitor of [3H]PTA binding, did not affect the [3H]MAZ binding process. This further supported the suggestion that while [3H]PTA binding sites are almost totally associated with the vesicular transporter for DA, [3H]MAZ does label a site involved in the DA-translocation across the neuronal membrane. The latter process seems to be rather insensitive to thyroid hypofunction, when however the intracellular storage of DA might be consistently impaired. In conclusion, PTA might be well exploited as a marker of the DA vesicular transporter through its molecular characterization, whenever possible.

Animals↗
PubMed1987

Peripheral dopamine receptors in the antihypertensive action of dihydroergotoxine in humans.

The effect of the intravenous administration of dihydroergotoxine (6 micrograms/kg) on arterial blood pressure, heart rate, and plasma concentrations of norepinephrine and 3,4-dihydroxyphenylacetic acid (the deaminated dopamine metabolite) was studied in 20 subjects with essential hypertension (8 men and 12 women aged 32-68 years old, World Health Organization Class I-II). In supine resting subjects, dihydroergotoxine significantly decreased systolic blood pressure (from 175 +/- 5 to 156 +/- 4 mm Hg; p less than 0.001), diastolic blood pressure (from 109 +/- 4 to 95 +/- 3 mm Hg; p less than 0.001), and heart rate (from 71 +/- 2 to 63 +/- 2 beats/min; p less than 0.001) as compared with the results of placebo treatment. Moreover, dihydroergotoxine reduced plasma levels of norepinephrine (from 368 +/- 39 to 238 +/- 33 pg/ml; p less than 0.001) and 3,4-dihydroxyphenylacetic acid (from 1.57 +/- 0.21 to 1.22 +/- 0.13 ng/ml; p less than 0.01). The time course of the blood pressure decrease paralleled that of plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine response to standing. The effect of domperidone, a peripheral presynaptic dopamine receptor antagonist, on dihydroergotoxine response was studied in six of the 20 subjects (3 men and 3 women 48-64 years old). The intravenous administration of domperidone (0.3 mg/kg) prevented the dihydroergotoxine-induced reduction in blood pressure and heart rate and the fall in plasma norepinephrine and 3,4-dihydroxyphenylacetic acid levels. Domperidone administered alone failed to significantly modify any measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Apomorphine hydrochloride-induced improvement in Huntington's chorea: stimulation of dopamine receptor.

Four patients affected by Huntington's chorea (HC) with a well defined family history of the disease were injected intramuscularly with apomorphine hydrochloride in nonemetic doses, ranging from 1 to 4 mg. Soon after treatment, all patients showed a marked decrease in abnormal involuntary movements. Pretreatment with haloperidol (2 mg intramuscularly) or sulpiride (100 mg intramuscularly) 30 minutes prior to apomorphine treatment, prevented the therapeutic effect of this compound. It is suggested that apomorphine-induced improvement in Huntington's Chorea is mediated by the stimulation of a special kind of dopamine receptor, leading to inhibition of the activity of dopaminergic neurons.

Adult↗