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G Battaglia

Publications and source records attributed to G Battaglia.

At least 19 recordsLinked to original sources
PubMed2004

Agonist-induced serotonin 2A receptor desensitization in the rat frontal cortex and hypothalamus.

This study examined the time course and possible mechanisms of agonist-induced desensitization of 5-hydroxytryptamine serotonin 2A receptors in the rat frontal cortex and hypothalamic paraventricular nucleus after 1, 4, and 7 days of treatment with (-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl [(-)-DOI] (1 mg/kg i.p.), a selective 5-HT(2A/2C) receptor agonist. In the frontal cortex, 5-HT-mediated phospholipase C (PLC) enzyme activity decreased by 24 to 30% after 4 to 7 days of (-)-DOI treatment without any significant changes in the guanosine 5'-3-O-(thio)triphosphate-mediated PLC enzyme activity. Additionally, treatment with (-)-DOI did not significantly change the levels of G(alpha11), regulator of G protein signaling (RGS)4, or RGS7 proteins in the frontal cortex, whereas G(alphaq) protein levels in the frontal cortex decreased (47%) only after 7 daily (-)-DOI injections. The functional status of 5-HT(2A) receptors in the hypothalamic paraventricular nucleus was examined using 5-HT(2A) receptor-mediated increases in plasma hormone levels. Plasma adrenocorticotrophic hormone (ACTH) and oxytocin measurements showed that 5-HT(2A) receptor desensitization began after only 1 day of (-)-DOI treatment, and the desensitization continued to increase after 4 and 7 days of treatment (ACTH response decreased 64.2-67.7%; oxytocin response decreased 82.3-90.1%). There were no significant alterations in levels of G(alphaq) or G(alpha11) lamic paraventricular proteins in the hypothanucleus. In conclusion, these results suggest that chronically administered (-)-DOI induces desensitization of 5-HT(2A) receptors in vivo, via a reduction in the ability of 5-HT(2A) receptors to activate G proteins without consistently altering levels of G(alpha) proteins or RGS proteins.

Amphetamines↗
PubMed2003

Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet.

Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg.kg-1.day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Chronic fluoxetine differentially affects 5-hydroxytryptamine (2A) receptor signaling in frontal cortex, oxytocin- and corticotropin-releasing factor-containing neurons in rat paraventricular nucleus.

Differential adaptive changes in serotonin2A [5-hydroxytryptamine (5-HT)2A] receptor signaling during treatment may be one mechanism involved in the latency of therapeutic improvement with antidepressants, such as fluoxetine. We examined the effects of fluoxetine (2, 3, 7, 21, or 42 days) on hypothalamic 5-HT2A receptor signaling. The hormone responses to an injection of the 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI) were used as an index of hypothalamic 5-HT2A receptor function. Treatment with fluoxetine for 21 or 42 days produced diminished adrenocorticotropic hormone (ACTH) and oxytocin (but not corticosterone) responses to DOI injections (2.5 mg/kg i.p.; 15 min postinjection). Regulators of G protein signaling 4 and Galphaq protein levels in the hypothalamic paraventricular nucleus were not altered during fluoxetine treatment. Because previous studies indicate that treatment with fluoxetine for 21 days resulted in increased hormone responses to DOI when measured at 30 min after injection, we examined the effect of fluoxetine (21 days) on DOI-induced increase hormone levels at 15, 30, and 60 min after DOI injection. Fluoxetine decreased the oxytocin response at 15 but not at 30 min post-DOI injection, and potentiated the ACTH and corticosterone responses at 30 min post-DOI injection. For comparison, we examined the effect of fluoxetine on 5-HT2A receptor-mediated increase in phospholipase C (PLC) activity in the frontal cortex. 5-HT-stimulated, but not guanosine 5'-O-(3-thio)triphosphate-stimulated PLC activity was increased after 21 days of fluoxetine-treatment. Overall, these results indicate that chronic fluoxetine treatment can potentiate 5-HT2A receptor signaling in frontal cortex but differentially alters 5-HT2A receptor signaling in oxytocin-containing neurons and corticotropin-releasing factor-containing neurons in the paraventricular nucleus.

Animals↗
PubMed2003

Endogenous activation of group-II metabotropic glutamate receptors inhibits the hypothalamic-pituitary-adrenocortical axis.

Systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), increased plasma corticosterone in mice to an extent similar to that induced by the despair test. Treatment with the mGlu2/3 receptor agonist, LY379268 (1 mg/kg, i.p.), or the non-competitive mGlu5 receptor antagonist, MPEP (5 mg/kg, i.p.), failed to induce significant changes in corticosterone levels. Searching for a site of action of LY341495, we examined the expression of mGlu receptor subtypes in the various anatomical regions of the mouse hypothalamic-pituitary-adrenal (HPA) axis. Only mGlu5 and -7 receptor mRNAs were detected in the adrenal gland by RT-PCR, whereas mGlu -1, -3, -4, -5, -7 and -8 receptor mRNAs were detected in the anterior pituitary. All transcripts (with the exception of mGlu5 and mGlu6 receptor mRNAs) were detected in the hypothalamus. However, Western blot analysis showed the presence of mGlu2/3 receptor proteins only in the hypothalamus and not in the anterior pituitary. This was consistent with functional data showing that LY341495 (0.1 and 1 microM) failed to affect ACTH secretion from isolated mouse anterior pituitaries. Moving from these observations, we examined whether LY341495 could activate the HPA axis by inhibiting mGlu2/3 receptors at hypothalamic level. We measured the release of corticotropin releasing hormone (CRH) in isolated mouse hypothalami incubated in the presence of subtype-selective mGlu receptor agonists or antagonists. Among all the drugs we have tested, only LY341495 was able to increase CRH secretion. With high concentrations of LY341495 (1 microM) this increase was similar to that induced by 50 mM K(+). The action of LY341495 was prevented by the combined application of the mGlu2/3 receptor agonist, LY379268. We conclude that group-II mGlu receptors tonically regulate the HPA axis by controlling CRH secretion at hypothalamic level.

Adrenal Glands↗
PubMed2003

(-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.

Group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) modulate neurotoxicity of excitatory amino acids and beta-amyloid-peptide (betaAP), as well as epileptic convulsions, most likely via presynaptic inhibition of glutamatergic neurotransmission. Due to the lack of subtype-selective ligands for group-III receptors, we previously utilized knock-out mice to identify mGluR4 as the primary receptor mediating neuroprotection of unselective group-III agonists such as L-AP(4) or (+)-PPG, whereas mGluR7 is critical for anticonvulsive effects. In a recent effort to find group-III subtype-selective drugs we identified (+/-)-PHCCC as a positive allosteric modulator for mGluR4. This compound increases agonist potency and markedly enhances maximum efficacy and, at higher concentrations, directly activates mGluR4 with low efficacy. All the activity of (+/-)-PHCCC resides in the (-)-enantiomer, which is inactive at mGluR2, -3, -5a, -6, -7b and -8a, but shows partial antagonist activity at mGluR1b (30% maximum antagonist efficacy). Chimeric receptor studies showed that the binding site of (-)-PHCCC is localized in the transmembrane region.Finally, (-)-PHCCC showed neuroprotection against betaAP- and NMDA-toxicity in mixed cultures of mouse cortical neurons. This neuroprotection was additive to that induced by the highly efficacious mGluR1 antagonist CPCCOEt and was blocked by MSOP, a group-III mGluR antagonist. Our data provide evidence for a novel pharmacological site on mGluR4, which may be used as a target-site for therapeutics.

Amyloid beta-Peptides↗
PubMed2002

Destruction of serotonergic nerve terminals prevents fluoxetine-induced desensitization of hypothalamic 5-HT(1A) receptors.

RATIONALE: Selective serotonin (5-HT, 5-hydroxytryptamine) reuptake inhibitors (SSRIs) such as fluoxetine produce a gradual desensitization of hypothalamic post-synaptic 5-HT(1A) receptor systems. It is assumed that the effects of SSRIs on post-synaptic 5-HT(1A) receptors are mediated by 5-HT reuptake inhibition, leading to an increase of 5-HT in the synapse. However, there is no direct evidence to support this hypothesis. OBJECTIVES: The present study determined whether 5-HT(1A) receptor desensitization was mediated by fluoxetine's effects on serotonergic nerve terminals. METHODS: Serotonergic nerve terminals were destroyed by intracerebroventricular (i.c.v.) injection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) combined with injection of the norepinephrine/dopamine reuptake inhibitor nomifensine. 5,7-DHT-induced loss of serotonergic terminals was confirmed by a 95% reduction in the density of [(3)H]paroxetine-labeled 5-HT transporters in the hypothalamus and a 97% reduction in the levels of 5-HT and 5-hydroxyindoleacetic acid in the cortex. Two weeks after the 5,7-DHT injections, rats were injected daily with fluoxetine (5 mg/kg or 10 mg/kg, i.p.) or saline for 14 days. RESULTS: Injections of 10 mg/kg fluoxetine produced a significant decrease in body weight gain. Destruction of serotonergic nerve terminals reduced body weight and potentiated the ability of fluoxetine to further inhibit body weight gain. Increases in plasma levels of adrenal corticotrophic hormone (ACTH, corticotropin), corticosterone, and oxytocin after injection of the 5-HT(1A) agonist 8-hydroxy-2-dipropylaminotetralin [(+/-)8-OH-DPAT] were used as peripheral markers of 5-HT(1A) receptor function in the hypothalamus. In vehicle-pretreated rats, fluoxetine produced a dose-dependent reduction in the (+/-)8-OH-DPAT-induced increase in plasma ACTH and oxytocin levels. Destruction of serotonergic nerve terminals blocked the ability of fluoxetine to produce a desensitization in the ACTH, corticosterone, and oxytocin responses to (+/-)8-OH-DPAT. CONCLUSIONS: The ability of fluoxetine to induce a desensitization of hypothalamic post-synaptic 5-HT(1A) receptor systems is dependent on the integrity of serotonergic nerve terminals in the hypothalamus, while its effect on body weight is not mediated by serotonergic nerve terminals in the hypothalamus.

5,7-Dihydroxytryptamine↗
PubMed2002

Continuous subcutaneous infusion of apomorphine rescues nigro-striatal dopaminergic terminals following MPTP injection in mice.

Apomorphine has been introduced in the treatment of late-stage Parkinson's Disease (PD). The disadvantage of a short half-life of apomorphine is now overcome by the use of a continuous subcutaneous (s.c.) self-delivering system. We examined whether continuous s.c. infusion of apomorphine rescues nigro-striatal dopaminergic neurons from toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Apomorphine was continuously infused in mice by means of a s.c. minipump that delivered the drug at a rate of 0.5 or 3.15 mg/kg/day. MPTP induced a >80% reduction in striatal dopamine (DA) after one day. DA levels were still substantially reduced one month following MPTP injection, in spite of a partial recovery. Similarly, striatal immunoreactivity for tyrosine hydroxylase and dopamine transporter was markedly reduced at this time interval. Continuous s.c. infusion of apomorphine starting 40 h following MPTP injection rescued striatal dopaminergic terminals, as assessed by measurements of DA and its metabolites, as well as TH and DAT immunostaining after one month. The neurorescuing effect was more remarkable at a delivery rate of 3.15 mg/kg/day of apomorphine. In contrast, no rescue was observed when apomorphine was administered as a single daily s.c. bolus of 1 or 5mg/kg starting 40 h following MPTP. We conclude that apomorphine is able to rescue nigro-striatal dopaminergic neurons when continuously delivered at doses that are comparable to those delivered by minipumps in PD patients. These results suggest that continuous s.c. infusion of apomorphine not only relieves the symptoms, but also reduce the ongoing degeneration of nigro-striatal dopaminergic neurons in PD patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Treatment of cycling female rats with fluoxetine induces desensitization of hypothalamic 5-HT(1A) receptors with no change in 5-HT(2A) receptors.

Although women constitute the majority of patients who receive treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, most animal studies of SSRIs are conducted on males. The present study investigated whether long-term treatment of cycling female rats with fluoxetine alters their estrous cycle and the sensitivity of hypothalamic serotonin (5-HT) 5-HT(1A) and 5-HT(2A) receptor systems. Adult female rats received daily injections of fluoxetine (10 mg/kg, i.p.) for three consecutive estrous cycles (15.2+/-0.2 days) with the first injection beginning on metestrus (when circulating estrogen levels are low and stable). Fluoxetine did not alter basal plasma estradiol levels at metestrus, nor did it alter the pattern of estrous cyclicity. Rats treated with fluoxetine showed a loss in body weight. On the morning of metestrus of the fourth cycle (18 h after the last fluoxetine injection), the rats were injected with a sub-maximal dose of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 50 MICRO/kg, s.c.) or a maximal dose of the 5-HT(2A) agonist [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] (DOI). Plasma levels of oxytocin, ACTH and corticosterone were measured as peripheral indicators of hypothalamic 5-HT(1A) and 5-HT(2A) receptor sensitivity. Injecting 8-OH-DPAT to saline pretreated rats produced a significant increase in plasma oxytocin (299%), ACTH (1456%) and corticosterone (170%) levels but not in plasma prolactin or renin concentrations. Greater increases in plasma levels of these hormones were observed after injecting DOI. Fluoxetine treatment completely blocked the oxytocin, ACTH and corticosterone responses to 8-OH-DPAT, but did not inhibit the effect of DOI on any hormone, thus confirming that fluoxetine treatment did not produce a deficit in the functioning of corticotropin releasing hormone or oxytocin containing neurons. These results indicate that in cycling female rats, fluoxetine treatment desensitizes hypothalamic post-synaptic 5-HT(1A) receptor signaling. Understanding the pharmacological effects of fluoxetine in females may lead to more effective treatment of women with mood disorders.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2002

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus.

BACKGROUND: Barrett's oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM: To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barrett's Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS: Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barrett's oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS: Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS: Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barrett's oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barrett's oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION: Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barrett's Oesophagus to develop.

Adult↗
PubMed2002

High-fiber diet supplementation in patients with irritable bowel syndrome (IBS): a multicenter, randomized, open trial comparison between wheat bran diet and partially hydrolyzed guar gum (PHGG).

High-fiber diet supplementation is commonly used in IBS, although it poses several management problems. Partially hydrolyzed guar gum (PHGG) has shown beneficial effects in animal and human studies, but its potential role in IBS symptom relief has not been evaluated yet. We investigated PHGG in IBS patients and compared it to a wheat bran diet. Abdominal pain, bowel habits, and subjective overall rating were longitudinally evaluated in 188 adult IBS patients (139 women and 49 men) for 12 weeks. Patients were classified as having diarrhea-predominant, constipation-predominant, or changeable bowel habits and were randomly assigned to groups receiving fiber (30 g/day of wheat bran) or PHGG (5 g/day). After four weeks, patients were allowed to switch group, depending on their subjective evaluation of their symptoms. Significantly more patients switched from fiber to PHGG (49.9%) than from PHGG to fiber (10.9%) at four weeks. Per protocol analysis showed that both fiber and PHGG were effective in improving pain and bowel habits, but no difference was found between the two groups. Conversely, intention-to-treat analysis showed a significantly greater success in the PHGG group (60%) than in the fiber group (40%). Moreover, significantly more patients in the PHGG group reported a greater subjective improvement than those in the Fiber group. In conclusion, improvements in core IBS symptoms (abdominal pain and bowel habits) were observed with both bran and PHGG, but the latter was better tolerated and preferred by patients, revealing a higher probability of success than bran and a lower probability of patients abandoning the prescribed regimen, suggesting that it can increase the benefits deriving from fiber intake in IBS, making it a valid option to consider for high-fiber diet supplementation.

Adult↗
PubMed2002

Morphological and biochemical evidence that apomorphine rescues striatal dopamine terminals and prevents methamphetamine toxicity.

Apomorphine, given by a single injection, repeated injections, or by continuous infusion, was tested for neuroprotective effects in mice administered methamphetamine or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce striatal dopamine (DA) depletion. In the first part of the study, the DA agonist (R)-apomorphine was administered at various doses (1, 5, and 10 mg/kg), 15 min before methamphetamine (5 mg/kg x 3, 2 h apart). Mice were sacrificed 5 days later. In the second part, apomorphine was administered either continuously by subcutaneous minipump (cumulative daily dose of 0.5, 1, and 3.15 mg/kg), or as single, repeated daily injections (up to 5 mg/kg) starting 40 h after an acute administration of MPTP (30 mg/kg). Mice were sacrificed at different time intervals (up to 1 month) following MPTP injection. In all the animals, the integrity of striatal DA terminals was evaluated by measuring striatal DA levels and TH immunohistochemistry. Apomorphine dose-dependently prevented methamphetamine toxicity. These effects were neither due to a decrease in the amount of striatal methamphetamine nor to the hypothermia, and they were not reversed by the DA antagonist haloperidol. Moreover, chronic, continuous (but not pulsatile) administration of apomorphine rescued damaged striatal dopaminergic terminals. These findings confirm a protective effect of apomorphine that also consists of a neurorescue of damaged striatal DA terminals. This suggests a new hypothesis about the long-term benefits observed during continuous apomorphine administration in Parkinson's disease patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Characterization of the functional heterologous desensitization of hypothalamic 5-HT(1A) receptors after 5-HT(2A) receptor activation.

Desensitization of 5-HT(1A) receptors could be involved in the long-term therapeutic effect of anxiolytic and antidepressant drugs. Pretreatment of rats with the 5-HT(2A/2C) agonist DOI induces an attenuation of hypothalamic 5-HT(1A) receptor-G(z)-protein signaling, measured as the ACTH and oxytocin responses to an injection of the 5-HT(1A) agonist 8-OH-DPAT. We characterized this functional heterologous desensitization of 5-HT(1A) receptors in rats and examined some of the mechanisms that are involved. A time course experiment revealed that DOI produces a delayed and reversible reduction of the ACTH and oxytocin responses to an 8-OH-DPAT challenge. The maximal desensitization occurred at 2 hr, and it disappeared 24 hr after DOI injection. The desensitization was dose-dependent, and it shifted the oxytocin and ACTH dose-response curves of 8-OH-DPAT to the right (increased ED(50)) with no change in their maximal responses (E(max)). The 5-HT(2A) receptor antagonist MDL 100,907 prevented the DOI-induced desensitization, indicating that 5-HT(2A) receptors mediate the effect of DOI. Analysis of the components of the 5-HT(1A) receptor-G(z)-protein signaling system showed that DOI did not alter the level of membrane-associated G(z)-proteins in the hypothalamus. Additionally, DOI did not alter the binding of [(3)H]8-OH-DPAT or the inhibition by GTPgammaS of [(3)H]8-OH-DPAT binding in the hypothalamus. In conclusion, the activation of 5-HT(2A) receptors induces a transient functional desensitization of 5-HT(1A) receptor signaling in the hypothalamus, which may occur distal to the 5-HT(1A) receptor-G(z)-protein interface.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

NMDA receptor subunits are phosphorylated by activation of neurotrophin receptors in PSD of rat spinal cord.

We have investigated the distribution of NMDA and neurotrophin receptor systems and their reciprocal interactions in post-synaptic densities (PSD) purified from spinal cord. NMDA receptor subunits, trkA and trkB, but not trkC, were present in spinal cord PSD. The incubation of PSD with BDNF and NGF induced the phosphorylation of NR2A and B subunits. This phosphorylation was counteracted by antibodies directed against the catalytic domain of trkA and trkB receptors and by genistein. These results suggest the existence of a previously unexplored cross-talk between neurotrophins and NMDA receptors in rat spinal cord neurons.

Animals↗
PubMed2001

Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage.

(R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease.

Animals↗
PubMed2001

Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission.

Selective antagonists of mGlu1 (LY367385 and CPCCOEt) and mGlu5 (MPEP) metabotropic glutamate receptors were neuroprotective against NMDA toxicity when either applied to mixed cortical cultures or locally infused into the caudate nucleus. Neuroprotection produced by LY367385 or CPCCOEt was occluded by GABA and was abolished by a cocktail of GABA(A) and GABA(B) receptor antagonists. In contrast, GABAergic drugs did not influence the action of MPEP. In microdialysis studies, LY367385 and CPCCOEt substantially enhanced GABA release in the corpus striatum of freely moving animals, whereas MPEP had no effect on GABA but abolished the stimulation of glutamate release induced by NMDA. A role for mGlu1 receptors in modulating GABAergic transmission was supported by electrophysiological studies carried out in cortico-striatal slices. In this particular model, the mixed mGlu1/5 receptor agonist, DHPG, reduced bicuculline-sensitive inhibitory postsynaptic currents presumably via a presynaptic mechanism. The action of DHPG was antagonized by LY367385, but not by MPEP. Taken together, these results indicate that selective blockade of mGlu1 receptors produces neuroprotection by enhancing GABAergic transmission.

Animals↗
PubMed2001

Computed tomography and magnetic resonance imaging of pathologic conditions of the middle ear.

Computed tomography (CT) is an excellent technique for demonstrating even small abnormalities of the thin and complex bony structures of the middle ear. For this reason, it is the modality of choice in the study of conductive hearing loss (CHL). However, not every patient complaining of CHL requires a CT study. In fact, established indications encompass complex conditions, such as the complications of acute and chronic otomastoiditis, the postoperative ear in chronic otomastoiditis or in the localization of prosthetic devices, and the assessment of congenital or vascular anomalies. Particularly, the precise extent of bone erosion associated with cholesteatoma is correctly demonstrated by high resolution CT. Conversely, although fistulization through the tegmen tympani or the posterior wall of temporal bone is usually detectable by CT, the actual involvement of meninges and veins are better assessed by magnetic resonance (MR). MR is also indicated when complicated inflammatory lesions are suspected to extend into the inner ear or towards the sigmoid sinus or jugular vein. Neoplasms arising from or extending into the middle ear require the use of both techniques as their combined data provide essential information. Most important data for surgical planning concern the destruction of thin bony structures and the relationships of the lesion with the dura and surrounding vessels. DSA and interventional vascular techniques maintain an essential role in the presurgical work-up and embolization of paragangliomas extended into the middle ear.

Cholesteatoma↗