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S Consolo

Publications and source records attributed to S Consolo.

At least 37 records · Page 2Linked to original sources
PubMed1995

Trans-synaptic modulation of striatal ACh release in vivo by the parafascicular thalamic nucleus.

Electrical stimulation of the parafascicular but not the ventrolateral or dorsomedial thalamic nucleus (ten 0.5 ms, 10 V pulses, 140 microA) of freely moving rats induced a frequency-dependent (2.5, 5, 10 and 20 Hz) increase in the extracellular acetylcholine (ACh) content of the dorsal striatum, assessed by trans-striatal microdialysis. The time-dependent effect of 10 Hz stimulation was studied. The peak increase, 39% above baseline, was attained during 4 min of stimulation. This was blocked by coperfusion with 5 microM tetrodotoxin, indicating that the release we measured represents a physiological process. The facilitatory effect of parafascicular nucleus stimulation does not appear to be associated with indirect action through the cerebral frontal cortex because acute lesion of the excitatory corticostriatal afferents, which by itself reduced basal ACh release by 40%, did not modify the effect of 10 Hz stimulation. The possible involvement of the fasciculus retroflexus in the facilitation of ACh release was also ruled out. The non-competitive NMDA-type receptor antagonist MK-801, applied by reversed dialysis (30 microM) or systemically injected (0.2 mg/kg), significantly reduced the basal ACh output and prevented the tetanus-evoked increase in ACh release. The results provide in vivo evidence that the activity of the cholinergic neurons in the dorsal striatum is trans-synaptically modulated by parafascicular nucleus excitatory afferents through activation of the NMDA subtype of glutamate receptors that is probably located in the striatum.

Acetylcholine↗
PubMed1995

Behavioral and biochemical changes after bilateral electrolytic lesions of the red nucleus of rat.

Bilateral electrolytic lesions of the red nucleus (RN) of rat decreased apomorphine-induced stereotypy, increased haloperidol-induced catalepsy, reversed apomorphine-induced hypothermy, decreased spiroperidol-induced hypomotility, and BHT-920-induced yawning and penile erection episodes. Moreover, apomorphine antagonized haloperidol-induced catalepsy in the RN-lesioned group. The lesioned animals revealed depleted levels of dopamine and its metabolites in brain areas as well as serotonin and its metabolite. The brain areas analyzed were pyriform cortex, substantia nigra, striatum, enthorinal cortex, and cerebellum. Based on these results, it is very likely that the RN has a complex role in the behavior of rats as a consequence of dopaminergic-serotoninergic changes in the central nervous system.

Animals↗
PubMed1995

Role of vesicular dopamine in the in vivo stimulation of striatal dopamine transmission by amphetamine: evidence from microdialysis and Fos immunohistochemistry.

The role of vesicular and newly synthesized dopamine in the action of amphetamine was investigated by studying the effect of reserpine and alpha-methyl-p-tyrosine pretreatment on amphetamine-induced changes in extracellular dopamine and acetylcholine, estimated by brain microdialysis, and on c-fos expression, estimated by quantitative immunohistochemistry of the Fos antigene, in the dorsal caudate-putamen of rats. Blockade of dopamine synthesis by alpha-methyl-p-tyrosine pretreatment (1 or 2 h) only partially prevented the increase in extracellular dopamine concentrations elicited by 0.5 and 2 mg/kg s.c. of amphetamine. Inactivation of vesicular amine uptake by reserpine pretreatment (3 h) reduced the increase in extracellular dopamine by 2 mg/kg but not by 0.5 mg/kg of amphetamine. Combined pretreatment with reserpine (3 h) and alpha-methyl-p-tyrosine (1 h) drastically reduced the increase in extracellular dopamine by both doses of amphetamine (0.5 and 2 mg/kg s.c.). alpha-Methyl-p-tyrosine pretreatment reduced c-fos expression stimulated by amphetamine (2 mg/kg) in the dorsomedial and dorsolateral caudate-putamen while reserpine pretreatment reduced it only in the dorsolateral caudate-putamen. Amphetamine (2 mg/kg s.c.) stimulated acetylcholine release but this effect was not modified by reserpine or alpha-methyl-p-tyrosine pretreatment. The results indicate that blockade of dopamine synthesis, by itself, is insufficient to prevent the stimulation of dopamine transmission by amphetamine and, conversely, that inactivation of vesicular dopamine significantly reduces amphetamine effects at pre- and postsynaptic levels. Therefore, vesicular dopamine appears to contribute to the stimulation of dopamine transmission elicited by amphetamine in the dorsal caudate-putamen.

Acetylcholine↗
PubMed1994

Impulse flow dependency of galanin release in vivo in the rat ventral hippocampus.

Using microdialysis and a sensitive RIA, we have studied the in vivo release of the neuropeptide galanin (GAL) from the ventral hippocampus of freely moving rats. The spontaneous outflow of GAL-like immunoreactivity (GAL-LI) (1.8 +/- 0.3 fmol per ml per 20 min) was dependent on the presence of extracellular Ca2+ and was inhibited by tetrodotoxin. Evoked release induced by infusion of KCl (60 mM) or veratridine (148 microM) was also Ca(2+)-dependent and sensitive to tetrodotoxin. Electrical stimulation of the ventral limb of the diagonal band nuclei induced a frequency-dependent (50-200 Hz) and tetrodotoxin-sensitive overflow of GAL-LI in the hippocampus. In vitro GAL-LI release (1.0 +/- 0.02 fmol per ml per 5 min), studied in slices of rat ventral hippocampus, was also Ca(2+)-dependent and was increased in a concentration-dependent manner by KCl depolarization. This study demonstrates the release of the neuropeptide GAL in the rat central nervous system. The in vivo release is related to the activity of the cholinergic GAL-LI-containing cells in the septal diagonal band nuclei. The results are discussed in relation to the coexistence of GAL and acetylcholine within the septal/diagonal band complex.

Animals↗
PubMed1994

5-HT4 receptor stimulation facilitates acetylcholine release in rat frontal cortex.

The effect of the serotonergic 5-HT4 receptor agonists BIMU 1 and BIMU 8 on in vivo acetylcholine (ACh) release in brain hemispheric regions of freely moving rats was investigated using the microdialysis technique. Both agonists, applied intracerebroventricularly, facilitated the release of ACh selectively in the frontal cortex and were ineffective in the striatum or dorsal hippocampus. The facilitatory effect of BIMU 1 in frontal cortex was prevented by the selective 5-HT4 receptor antagonists GR 125487 and GR 113808 which by themselves did not alter basal release. the results provide the first evidence that serotonin facilitates ACh release in frontal cortex through stimulation of 5-HT4 receptors which are not tonically activated. 5-HT4 receptor agonists might thus offer a novel means of boosting central cholinergic function to overcome the cholinergic deficit in memory disorders.

Acetylcholine↗
PubMed1994

Improved local control and survival with the "sandwich" technique of pelvic radiotherapy for resectable rectal cancer. A retrospective, multivariate analysis.

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy group vs. 7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P = 0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P = 0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.

Adult↗
PubMed1994

Nerve-sparing surgery in 302 resectable rectosigmoid cancer patients: genitourinary morbidity and 10-year survival.

PURPOSE: The aim of this study was to evaluate 5-year and 10-year disease-free survival, urinary dysfunction, and sexual activity after nerve-sparing radical surgery, including lumboaortic lymphadenectomy for rectosigmoid cancer. METHODS: Since 1980 to 1992, 302 consecutive patients affected with rectal (188) or sigmoid (114) resectable cancer underwent radical surgery. Lumboaortic lymphadenectomy was routinely performed and total mesorectal dissection was always accomplished in rectal cancer. Splanchnic nerves, superior hypogastric plexus, hypogastric nerves, and sacral parasympathetic nerves were sought, identified, and preserved or, when necessary, unilaterally sacrificed. Fifty-three (17.6 percent) patients were classified Dukes A, 145 (48.0 percent) B, 46 (15.2 percent) C1, and 17 (5.6 percent) C2. Thirty-nine (12.9 percent) patients were Dukes D. In 85 rectal cancer patients, tumor was located at the lower third. Eighty-six of 210 Dukes B and C patients were submitted to systemic chemotherapy and/or high-dose pelvic radiotherapy. RESULTS: The actuarial 5-year disease-free survival was 58.5 percent in rectal and 65.7 percent in sigmoid cancer patients, median follow-up time was 47 months. During the follow-up, each patient was interviewed about sexual activity and urinary dysfunction and a questionnaire was filled out. Urinary dysfunction was not frequently observed, while a definitive sexual impotence was reported in 27.6 percent of the patients. The age under 60 years and sphincter-saving surgery were demonstrated as significantly contributing to retaining a satisfactory sexual activity. CONCLUSIONS: Unexpectedly high disease-free survival was observed in the Dukes C2 subgroup. It allows us to hypothesize that lumboaortic lymphadenectomy could remove neoplastic microfoci present at this level in those patients, enhancing surgical chances of cure. The majority of male patients under 60 years old can retain a satisfactory sexual activity after undergoing a nerve-sparing sphincter-saving cancer surgery.

Adult↗
PubMed1994

Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions.

The striatum is viewed as a structure performing fast neurotransmitter-mediated operations through somatotopically organized projections to medium-size spiny neurons. This view is contrasted with another view that depicts the striatum as a site of diffuse modulatory influences mediated by cholinergic interneurons and by dopamine and N-methyl-D-aspartate receptors. These two operational and organizational modes both contribute, through their mutual interaction, to the function of basal ganglia. Detailed knowledge of the neural mechanisms by which such interactions take place and are expressed into behaviour, can provide new insight into the physiopathology and new clues for therapy of disorders of basal ganglia.

Acetylcholine↗
PubMed1994

Serotonergic facilitation of acetylcholine release in vivo from rat dorsal hippocampus via serotonin 5-HT3 receptors.

The serotonin (5-HT) releaser d-fenfluramine and its active metabolite d-norfenfluramine, or the 5-HT-uptake inhibitor citalopram, by increasing synaptic 5-HT availability, facilitated in vivo release of acetylcholine (ACh) from dorsal hippocampi of freely moving rats as determined by the microdialysis technique. The effects of d-norfenfluramine (7.5 mg/kg i.p.) and citalopram (10 microM, applied by reverse dialysis) were prevented by a 14-day chemical lesion of the raphe nuclei, suggesting mediation by the 5-HT system in the cholinergic action of the drugs. The increase in extracellular ACh content induced by d-norfenfluramine (5 mg/kg i.p.) was antagonized by the 5-HT3 receptor antagonists tropisetron (0.5 mg/kg i.p.) and DAU 6215 (60 micrograms/kg i.p.), but not by the mixed 5-HT1 and 5-HT2 receptor antagonist metergoline (2 mg/kg s.c.). In accordance with an involvement of the 5-HT3 receptor in the ACh facilitation induced by d-norfenfluramine is the finding that the selective 5-HT3 receptor agonist 2-methylserotonin (250 micrograms i.c.v., or 10 microM applied by reverse dialysis) raised ACh release. The effect of the intracerebroventricular drug was prevented by the 5-HT3 antagonists DAU 6215 (60 micrograms/kg i.p.) and ondansetron (60 micrograms/kg s.c.). These antagonists by themselves did not modify the basal ACh release, indicating that 5-HT does not tonically activate the 5-HT3 receptors involved. In conclusion, the overall regulatory control exerted by 5-HT in vivo is to facilitate hippocampal ACh release. This is mediated by 5-HT3 receptors probably located in the dorsal hippocampi.

Acetylcholine↗
PubMed1993

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.

Amino Acid Sequence↗
PubMed1993

Neuroleptics increase striatal acetylcholine release by a sequential D-1 and D-2 receptor mechanism.

In normal striata, pre-treatment with the D-1 antagonist SCH 23390 (250 and 25 micrograms kg-1, s.c.) completely and lastingly prevented the D-2 antagonist remoxipride (REM) from increasing acetylcholine (ACh) release; post-treatment did not affect REM action. In alpha-methyl-p-tyrosine (alpha-MpT) dopamine (DA)-depleted striata, however, pretreatment with SCH 23390 resulted in a transient impairment of REM induced stimulation of ACh release but post-treatment still had no effect. Two different mechanisms therefore seem to be involved in D-2 antagonist-induced stimulation of ACh release; the antagonists indirectly activate a D-1 receptor-mediated facilitatory mechanism regulating cholinergic function, and directly block a D-2 receptor-mediated inhibitory one. In normal rats, in an early phase after D-2 antagonist administration, only the first mechanism is operative; in a later phase, both mechanisms cooperate in the stimulation of ACh release. When DA release is impaired by alpha-MpT, the D-2 inhibitory receptor mechanism becomes more important than the D-1 facilitatory one in controlling ACh release.

Acetylcholine↗
PubMed1993

N-terminal galanin fragments inhibit the hippocampal release of acetylcholine in vivo.

Using synthetic N-terminal fragments of galanin, galanin (1-7), galanin (1-9), galanin (1-12) and galanin (1-16), we have shown that the minimal sequence required for inhibition of acetylcholine release in vivo from rat ventral hippocampus corresponds to galanin (1-12). The fragment (1-9) displays activity in vivo but only at a very high concentration of 6.23 nmol while galanin (1-7) and C-terminal fragment (17-29) are without effect. Binding studies showed that galanin (1-16) and galanin (1-12) bind with submicromolar IC50 values to rat hippocampal galanin receptors. Galanin (1-9) has substantially lower affinity towards rat ventral hippocampal galanin receptor.

Acetylcholine↗
PubMed1993

Mechanical deafferentation of basal forebrain-cortical pathways and neurotoxic lesions of the nucleus basalis magnocellularis: comparative effect on spatial learning and cortical acetylcholine release in vivo.

Rats were assigned to one of the following treatments: bilateral cut of basal forebrain-cortical fibers (DEAFF), ibotenic (IBO) or quisqualic (QUIS) acid lesions of the NBM and sham operations (SHAM). They were trained to perform a radial eight-arm maze task with all the paths or only four paths baited. Cortical cholinergic release measured by microdialysis in vivo and choline acetyltransferase activity were also assessed in the four lesion conditions. The results show that, in the full baited maze task, only the DEAFF group showed a severe spatial learning impairment. In the four-baited path task, the DEAFF group was still more impaired than the other groups but a performance deficit also emerged in rats with IBO lesions. Neurochemical data indicated that cortical choline acetyltransferase activity was reduced by 25% after IBO lesions, by 52% after DEAFF and by 46% after Quis lesions. However, cortical cholinergic release, which dropped in the same fashion after DEAFF or QUIS lesions, was unaffected by IBO lesions. Thus, in spite of the distinctive patterns of behaviour exhibited by the three lesioned groups, no correlation between cortical cholinergic deficiencies and spatial learning impairment was found. The similar behavioural effects produced by DEAFF and fornix sections suggests that, among the basal forebrain-cortical pathways, descending fibers projecting onto the septo-hippocampal system could exert a strong control on spatial learning performance.

Acetylcholine↗
PubMed1993

Differences between rat dorsal and ventral hippocampus in muscarinic receptor agonist binding and interaction with phospholipase C.

Carbachol, a full muscarinic receptor agonist, stimulated [3H]inositol phosphate accumulation in both the ventral and dorsal hippocampus, but its efficacy and affinity were higher in the former area. The partial agonist oxotremorine had a weak stimulatory effect in both regions. The affinity profiles of pirenzepine and AF-DX 116 in antagonizing carbachol-stimulated [3H]inositol phosphate accumulation indicated that M1 and M3 receptors contributed equally to the response in either region. On the other hand, there were no differences in the receptor density, or in the distribution of muscarinic receptor subtypes between the two regions of the hippocampus which could account for the effect as determined in binding experiments with selective antagonists. Analysis of carbachol binding curves did, instead, indicate a difference in the way the agonist interacted with the receptors within the hippocampus, i.e., carbachol recognized three agonist affinity states (superhigh, high and low) in the ventral hippocampus, and only two (high and low) in the dorsal part. The findings thus suggested that the regional diversity in the efficacy of carbachol in stimulating phosphoinositide turnover was related to the complexity with which it bound to muscarinic receptors. Transduction processes that intervene between changes in the muscarinic receptors' conformation and activation of phospholipase C might be relevant to these differences.

Alkaloids↗
PubMed1993

Stimulation of dopamine transmission in the dorsal caudate nucleus by pargyline as demonstrated by dopamine and acetylcholine microdialysis and Fos immunohistochemistry.

The effect of pargyline on dopamine neurotransmission was investigated by trans-striatal microdialysis combined with Fos immunohistochemistry. Pargyline, 75 mg/kg i.p., increased dopamine and acetylcholine output while drastically decreased dopamine deaminated metabolites. Administration of pargyline resulted in the appearance of Fos-positive nuclei distributed along a gradient around the dialysis probe. Pretreatment with the D1 antagonist SCH 23390 potentiated the effect of pargyline on dopamine output while preventing that on acetylcholine output and on Fos formation. Similarly, lack of calcium in the perfusion medium abolished the effect of pargyline on dopamine and acetylcholine output and on Fos formation. In rats not implanted with dialysis probes pargyline administration resulted in only rare Fos-positive nuclei in the dorsal caudate. The present study indicates that pargyline stimulates dopamine transmission in the dorsal caudate in the area around the dialysis probe but not distant from the fibre or in unimplanted rats. This effect appears to reflect an interaction between the drug-induced changes and those locally elicited by the probe.

Acetylcholine↗
PubMed1992

Mechanism of the galanin induced increase in acetylcholine release in vivo from striata of freely moving rats.

Galanin (GAL) administered intracerebroventricularly (i.c.v.) induced a strong and long-lasting increase in the basal acetylcholine (ACh) release from striata of freely moving rats only when the excitatory corticostriatal input was removed, while its effect was transient in striata of sham-operated rats. This effect was dose-dependent (0.78, 1.56 and 3.12 nmol) and was completely prevented by the GAL receptor antagonist, galantide. GAL injected locally (3.12 nmol) in deafferented striata also induced a persistent increase in ACh release although to a lower extent. The impairment of monoaminergic neurotransmission caused by alpha-methylparatyrosine or p-chlorophenylalanine, respectively inhibitors of catecholamine and serotonin synthesis, completely prevented the rise in ACh output from deafferented striata while the muscarinic antagonist, scopolamine (0.5 mg/kg, s.c.), failed to do it. The data suggest that GAL in the deafferented striatum facilitates basal ACh release through an indirect mechanism. The effect seems to be at least partly mediated by an action of GAL on specific receptors in the striata.

Acetylcholine↗
PubMed1992

Galanin reduces PDBu-induced protein phosphorylation in rat ventral hippocampus.

The effect of galanin (GAL) on basal and phorbol-12,13-dibutyrate (PDBu) induced protein phosphorylation in rat ventral hippocampal miniprisms was investigated. GAL (0.5, 1 and 2 microM) inhibited PDBu stimulation in a concentration-dependent manner without altering basal protein phosphorylation. This inhibitory effect was prevented by the GAL antagonist galantide. GAL did not affect either the activity of protein kinase C (PKC) from rat brain or basal phosphorylation in ventral hippocampal hippogenates, suggesting that it did not directly modulate PKC activity. Depolarization of miniprisms from ventral hippocampi by 18 mM K+ prevented the effect of GAL on PDBu-induced phosphorylation. The results indicate that GAL indirectly regulates neuronal protein phosphorylation by a GAL receptor-mediated action.

Animals↗