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Biomedical subjects

M Carli

Publications and source records attributed to M Carli.

At least 73 records · Page 4Linked to original sources
PubMed1996

Alkylation of [3H]8-OH-DPAT binding sites in rat cerebral cortex and hippocampus.

The binding of tritiated 8-hydroxy-2-(di-n-propyl-amino)tetralin, or [3H]8-OH-DPAT, to membranes from rat cerebral cortex and hippocampus could be inhibited by serotonin (5-HT) and buspirone, and by the 5-HT antagonists propranolol, NAN-190, pindolol, pindobind-5-HT(1A), WAY1OO135, spiperone and ritanserin. All competition curves, except for ritanserin, best fitted a two-site model. In vitro treatment of the membranes with N-ethylmaleimide (NEM), to alkylate sulfhydryl groups, caused dose-dependent decreases of binding; the inhibition curves were biphasic, and the effects irreversible. Reduction of disulfide bonds with L-dithiothreitol (L-DTT) also decreased binding, but in a monophasic way; these effects were fully reversible in cortex, but only partially reversible in hippocampus. In the latter region, but not in cerebral cortex, previous occupancy by [(3)H]8-OH-DPAT partially protected binding from the effects of both L-DTT and NEM, suggesting that the thiol groups in the receptor recognition site(s) of this brain region are readily accessible. The binding characteristics were examined with the aid of saturation curves, carried out with increasing concentrations, up to 140 nM, of [(3)H]8-OH-DPAT. The saturation data were suggestive of a two-site receptor model incorporating a high-affinity site (K(H) of 0.3-0.5 nM) corresponding to the 5-HT(1A) receptor, and a low-affinity site (KL of ca 25 nM). After in vivo alkylations, carried out by treating rats with N-ethoxycarbonyl-2-ethoxy-1,2-dihydro-quinoline (EEDQ), the saturation curves from both control and EEDQ-treated rats were again best fitted to a two-site model. For EEDQ-treated animals, a drastic decrease of 5-HT(1A) receptor binding activity was noted; this loss was greater in hippocampus than in cerebral cortex. Since the decrease in 5-HT(1A) receptors was not associated with changes in low-affinity binding, the results suggest independent regulations of the two [(3)H]8-OH-DPAT binding proteins. Altogether, the present data further supports the notion that [(3)H]8-OH-DPAT, besides labelling 5-HT(1A) receptors, also binds to other structures in rat cerebral cortex and hippocampus.

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

Response of previously untreated metastatic rhabdomyosarcoma to combination chemotherapy with carboplatin, epirubicin and vincristine.

This study aimed to assess the response to a novel combination chemotherapy containing carboplatin plus epirubicin in previously untreated children with metastatic rhabdomyosarcoma. 81 children (< or = 18 years) were treated between 1989 and 1994 with a combination of carboplatin, epirubicin and vincristine, given as initial therapy as part of a multicentre European trial (SIOP Intergroup Study of Stage IV Malignant Mesenchymal Tumours in Children). The chemotherapy regimen (CEV) was: carboplatin 500 mg/m2 plus epirubicin 150 mg/m2 administered on day 1, and vincristine 1.5 mg/m2 administered on days 1 and 7. Response was evaluated at day 21. 2 patients achieved complete remission and 41 patients partial remission, with an overall response rate of 53% (95% confidence interval 45-76%). Three patients showed progressive disease (4%). Toxicity was mainly haematological, with 52% experiencing grade IV neutropenia and 34% grade IV thrombocytopenia. Mucositis and infections were not severe. There were no toxic deaths. The combination of carboplatin, epirubicin and vincristine is effective and well tolerated in patients with metastatic rhabdomyosarcoma.

Adolescent↗
PubMed1996

[3H]8-OH-DPAT binding and serotonin content in rat cerebral cortex after acute fluoxetine, desipramine, or pargyline.

Cortical serotonin1A (5-HT1A) receptors in the rat were studied following acute (24 hours) intraperitoneal administrations of the 5-HT uptake inhibitor fluoxetine (10 mg/kg), the antidepressant desipramine (20 mg/kg), or the monoamine oxidase (MAO) inhibitor pargyline (75 mg/kg). The 5-HT1A receptors were labelled in total cortex membrane homogenates with [3H]8-OH-DPAT, and the monoamines measured in cingulate cortex by high-performance liquid chromatography. As expected, after pargyline administration tissue concentrations of 5-HT, noradrenaline (NA) and dopamine (DA) were markedly increased due to MAO inhibition with a concomitant decrease of the metabolites 5-hydroxyindole-3-acetic acid and homovanillic acid. However, neither desipramine nor fluoxetine changed monoamine concentrations. Saturation binding with [3H]8-OH-DPAT revealed that, for the control animals (saline treated), the curves were best fitted to a 2-site model. Following drug administration, the saturation curves were still best fitted to a 2-site model, with no changes in affinities or bonding capacities. In competition experiments with 5-HT, buspirone, and pindolol, the curves were always best fitted to a 2-site model. Following fluoxetine administration, the inhibition curves revealed decreases in the affinity of the low-affinity site (KiL) for the agonist buspirone, and in the relative proportion of these sites. In addition, following pargyline, there was an increase in the affinity of the high-affinity site (KiH) for 5-HT but with a decrease of the relative proportion of high-affinity sites. The results confirm that [3H]8-OH-DPAT binding is to a 2-site model, and reveal an absence of downregulation of 5-HT1A receptors following increases in tissue 5-HT after MAO inhibition or antidepressant administrations. Moreover, the data may reflect an alteration of the coupling efficacy between cortical 5-HT1A receptors and their associated G proteins.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

(S)-WAY 100135, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine.

Scopolamine, 3.75 micrograms/microliters infused bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy but had no effect on choice latency or errors of omission in rats trained in a two-platform spatial discrimination task. Administered subcutaneously at 3 and 10 mg/kg 30 min before each training session, N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanami de dihydrochloride ((S)-WAY 100135), a 5-HT1A receptor antagonist, prevented the impairment of choice accuracy induced by intrahippocampal scopolamine. No subcutaneous dose of (S)-WAY 100135 by itself modified the acquisition of spatial learning. Administered into the dorsal hippocampus 15 min before each training session, (S)-WAY 100135 at doses of 0.2, 1 and 5 micrograms/microliters did not affect the acquisition of spatial learning but dose dependently prevented the impairment of choice accuracy caused by scopolamine, 3.75 micrograms/microliters infused into the same area. These findings suggest that blockade of 5-HT1A receptors can compensate the loss of cholinergic excitatory input on pyramidal cells, probably by favouring the action of other excitatory transmitters.

Animals↗
PubMed1995

Autoimmune enteropathy with anti-goblet cell antibodies.

A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.

Autoantibodies↗
PubMed1995

8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus.

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa, induction regimen in advanced neuroblastoma: preliminary results. Italian Neuroblastoma Cooperative Group.

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.

Adolescent↗
PubMed1995

Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.

PURPOSE: To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS: Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS: Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION: Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.

Adolescent↗
PubMed1994

Second malignant tumors after elective end of therapy for a first cancer in childhood: a multicenter study in Italy.

To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of Pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,310 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor.

Adolescent↗
PubMed1994

Effects of chronic lithium treatments on central dopaminergic receptor systems: G proteins as possible targets.

Numerous biochemical and electrophysiological studies have proposed a role for dopamine (DA) in the therapeutic efficacy of lithium (Li+) salts. The effects of ex vivo chronic Li+ treatments on neostriatal DA receptors, as well as on the G protein adenylyl cyclase complex and on tissue cAMP levels were investigated in adult rats. The animals were administered LiCl in their drinking water (1 g/l) for varying periods of time, i.e. 1, 15 and 28 days. After sacrifice by decapitation, their brains were removed and the neostriatum dissected out to assay DA receptors and adenylyl cyclase activity. The antagonists [3H]SCH23390 and [3H]raclopride were employed to label D1 and D2 receptors, respectively. Chronic Li+ treatments did not modify the saturation binding of either ligand. However, competition studies of the same antagonists by DA revealed biphasic curves, and the inhibition constant of the high-affinity site was significatively increased after chronic Li+. The data suggest an alteration in the coupling efficacy between G proteins and DA receptors. Moreover, chronic (28 day) Li+ treatment, but not a 1 day Li+ administration, lead to a reduction of the GTP-induced and DA-sensitive adenylyl cyclase activity, without changes in the basal activity or in forskolin-induced cAMP production. The results demonstrate that chronic Li+ treatments diminish neostriatal dopaminergic activity, probably through a direct action on the G protein itself. The underlying mechanisms do not appear to involve modifications in either the D1 or the D2 receptor primary ligand recognition sites, but may represent alterations in both the coupling process and the capacity of the G proteins, once activated, to stimulate adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1994

Heterogeneity of cortical and hippocampal 5-HT1A receptors: a reappraisal of homogenate binding with 8-[3H]hydroxydipropylaminotetralin.

The selective serotonin (5-HT) agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT) has been extensively used to characterize the physiological, biochemical, and behavioral features of the 5-HT1A receptor. A further characterization of this receptor subtype was conducted with membrane preparations from rat cerebral cortex and hippocampus. The saturation binding isotherms of [3H]8-OH-DPAT (free ligand from 200 pM to 160 nM) revealed high-affinity 5-HT1A receptors (KH = 0.7-0.8 nM) and low-affinity (KL = 22-36 nM) binding sites. The kinetics of [3H]8-OH-DPAT binding were examined at two ligand concentrations, i.e., 1 and 10 nM, and in each case revealed two dissociation rate constants supporting the existence of high- and low-affinity binding sites. When the high-affinity sites were labeled with a 1 nM concentration of [3H]8-OH-DPAT, the competition curves of agonist and antagonist drugs were best fit to a two-site model, indicating the presence of two different 5-HT1A binding sites or, alternatively, two affinity states, tentatively designated as 5-HT1AHIGH and 5-HT1ALOW. However, the low correlation between the affinities of various drugs for these sites indicates the existence of different and independent binding sites. To determine whether 5-HT1A sites are modulated by 5'-guanylylimidodiphosphate, inhibition experiments with 5-HT were performed in the presence or in the absence of 100 microM 5'-guanylylimidodiphosphate. The binding of 1 nM [3H]8-OH-DPAT to the 5-HT1AHIGH site was dramatically (80%) reduced by 5'-guanylylimidodiphosphate; in contrast, the low-affinity site, or 5-HT1ALOW, was seemingly insensitive to the guanine nucleotide. The findings suggest that the high-affinity 5-HT1AHIGH site corresponds to the classic 5-HT1A receptor, whereas the novel 5-HT1ALOW binding site, labeled by 1 nM [3H]8-OH-DPAT and having a micromolar affinity for 5-HT, may not belong to the G protein family of receptors. To further investigate the relationship of 5-HT1A sites and the 5-HT innervation, rats were treated with p-chlorophenylalanine or with the neurotoxin p-chloroamphetamine. The inhibition of 5-HT synthesis by p-chlorophenylalanine did not alter either of the two 5-HT1A sites, but deafferentation by p-chloroamphetamine caused a loss of the low-affinity [3H]8-OH-DPAT binding sites, indicating that these novel binding sites may be located presynaptically on 5-HT fibers and/or nerve terminals.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Paratesticular rhabdomyosarcoma (RMS) and paraaortic lymphadenectomy.

This study is based on the experience of the Italian Cooperative Studies "AIEOP-RMS 79 and RMS 88". Between October 1979 and December 1989 299 children under 15 years of age with a histologically proven rhabdomyosarcoma (RMS) were examined. We analyzed the problem of the paratesticular localization paying particular attention to the role of surgery in dealing with paraaortic nodes. In the first study (RMS 79) the surgical exploration of retroperitoneal nodes was required: this procedure performed in 11 out of 14 patients affected by paratesticular RMS confirmed the negative data observed with diagnostic investigations. In RMS 88 study the sampling of retroperitoneal nodes was not required in cases with negative radiological findings but suggested in those cases with uncertain signs; two out of 8 patients underwent a laparotomy. In these two cases the results were negative. These 22 children were treated with an adjuvant chemotherapy after surgery and at present they show no evidence of disease.

Adolescent↗
PubMed1994

Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors.

Insulin-like growth factor II (IGF-II) is a mitogen for many cell types and an important modulator of muscle growth and differentiation. IGF-II gene is prevalently expressed during prenatal development and its gene activity is regulated by genomic imprinting, in that the allele inherited from the father is active and the allele inherited from the mother is inactive in most normal tissues. IGF-II expression is activated in several types of human neoplasms and an alteration of IGF-II imprinting has been described in Beckwith-Wiedemann syndrome and Wilms' tumor. Here we show that monoallelic expression of IGF-II gene is conserved in normal adult muscle tissue whereas two or more copies of active IGF-II alleles, arising by either relaxation of imprinting or duplication of the active allele, are found in 9 out of 11 (82%) rhabdomyosarcomas retaining heterozygosity at 11p15, regardless of the histological subtype. Since IGF-II has been indicated as an autocrine growth factor for rhabdomyosarcoma cells, these findings strongly suggest that acquisition of a double dosage of active IGF-II gene is an important step for the initiation or progression of rhabdomyosarcoma tumorigenesis. Among different types of muscle tumors, relaxation of imprinting seems to arise prevalently in rhabdomyosarcomas, since we have detected only one case of partial reactivation of the maternal IGF-II allele out of 7 leiomyosarcomas tested.

Adult↗
PubMed1994

Therapy associated differentiation in rhabdomyosarcomas.

The morphologic and immunophenotypical features of three embryonal and one spindle cell rhabdomyosarcomas that underwent marked cytologic differentiation after polychemotherapy are described. In all the cases the morphologic changes were associated to disappearance of vimentin immunoreactivity and intense positivity for desmin, muscle specific actins, and myoglobin; in addition the differentiated tumor cells acquired a strong and continuous pericellular staining for laminin. The mitotic activity was significantly decreased. Drug associated differentiation seems to recapitulate the normal myogenic development to the point that the more mature neoplastic cells may represent terminally differentiated elements withdrawn from cell cycle. However, due to the persistence of a small number of poorly differentiated rhabdomyoblasts, the clinical consequences of this phenomenon are unclear.

Actins↗
PubMed1993

Treatment of pediatric Hodgkin disease tailored to stage, mediastinal mass, and age. An Italian (AIEOP) multicenter study on 215 patients.

BACKGROUND: Attempting to optimize treatment results in pediatric Hodgkin disease while minimizing major side effects, at least in early-stage patients, in 1983 the Italian Association of Pediatric Hematology and Oncology (AIEOP) conceived a multicenter study tailored according to stage, bulky mediastinal mass, and age. METHODS: Between December, 1983 and January, 1989, 215 evaluable patients (median age, 9.9 years, range, 1-15 years) received the AIEOP-MH 1983 Hodgkin disease protocol of low-dose radiation therapy (20-25 Gy), with three cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) for children with early-stage and favorable disease, and with alternating cycles of an eight non-cross-resistant drug combination regimen (nitrogen mustard, vincristine, procarbazine, and prednisone [MOPP]/ABVD) for 6 months for those with bulky and unfavorable disease. Patients in advanced stages received four additional courses of MOPP/ABVD as maintenance therapy. RESULTS: The overall survival and freedom from progression (FFP) probabilities at 7 years are 85.7% and 81.5% respectively. FFP probabilities at 7 years in Groups 1 (58 patients in Stages I and IIA with mass/thorax [M/T] < 0.33), 2 (56 patients in Stages IEA, IB, IIA with M/T > 0.33, IIB, and IIIA), and 3 (38 patients in Stages IIIB and IVA and B) were 94.8%, 81.4%, and 60.3%, respectively. Multivariate analysis showed B symptoms, M/T > 0.33, and stage to be significant, independent prognostic factors affecting survival and FFP curves. CONCLUSIONS: The encouraging results in early-stage disease indicate the validity of using less toxic treatment in this subgroup to maximize quality of life. Patients with bulky mediastinal disease tended to fare worse than those with M/T < 0.33 or without mediastinal involvement (FFP at 7 years: 69.4% versus 93.3%) and showed early local recurrence. In advanced stages, the eight-drug combination regimen (MOPP/ABVD) plus low-dose radiation therapy provided no major improvement in outcome; here, alternative chemotherapeutic regimens should be tested in a large, randomized, clinical trial to evaluate their efficacy and determine the frequency of delayed toxicity.

Adolescent↗
PubMed1993

Stimulation of hippocampal 5-HT1A receptors causes amnesia and anxiolytic-like but not antidepressant-like effects in the rat.

Administration of 2 and 5 but not 0.4 microgram/microliter 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the CA1 region of the dorsal hippocampus 10 min before the acquisition trial in a passive avoidance task significantly reduced retention latencies 24 h later. The effect of 5 micrograms 8-OH-DPAT on retention latencies was completely antagonized by 1 microgram/microliter spiroxatrine, a 5-HT1A receptor antagonist, infused into the dorsal hippocampus 5 min before 8-OH-DPAT. Administered 5 min after the acquisition trial, 5 micrograms/microliters 8-OH-DPAT had no effect on retention latencies 24 h later. Administration of 5 micrograms/microliters 8-OH-DPAT into the dorsal hippocampus did not significantly change the thresholds for responses to the same electrical stimuli used in the passive avoidance task and had no antidepressant-like effect in the forced swimming test. The dose of 5 micrograms/microliters 8-OH-DPAT administered into the dorsal hippocampus caused anxiolytic-like effects assessed by stress-induced deficit in open field locomotor activity. The results suggest that stimulation of 5-HT1A receptors in the dorsal hippocampus impairs rats' performance in a passive avoidance task by interfering with memory processes or by attenuating the emotional impact of the shock through an anxiolytic action.

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