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L Fattore

Publications and source records attributed to L Fattore.

At least 19 recordsLinked to original sources
PubMed2003

Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats.

Because opioid and cannabinoid systems have been reported to interact in the modulation of addictive behaviour, this study was aimed at investigating the ability of cannabinoid agents to reinstate or prevent heroin-seeking behaviour after a prolonged period of extinction. In rats previously trained to self-administer heroin intravenously, non-contingent non-reinforced priming administrations of heroin and cannabinoids were presented after long-term extinction, and lever pressing following injections was observed. Results showed that: (i) intravenous priming infusions of heroin (0.1 and 0.2 mg/kg) lead to reinstatement of drug-seeking behaviour; (ii) intraperitoneal priming injections of the central cannabinoid receptor agonists R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazinyl) (1-naphthalenyl)methanonemesylate (WIN 55,212-2, 0.15 and 0.3 mg/kg) and (-)-cis-3-[2-hydroxy-4(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940, 0.05 and 0.1 mg/kg), but not delta9-tetrahydrocannabinol (delta9-THC, 0.1-1.0 mg/kg), effectively restored heroin-seeking behaviour; (iii) intraperitoneal priming injection of the central cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)4-methyl-1H-pyrazole-3-carboxamide (SR 141716A, 0.3 mg/kg) did not reinstate responding, but (iv) completely prevented heroin-induced reinstatement of drug-seeking behaviour. Moreover, heroin-seeking behaviour was still present for a few days following cannabinoid primings, indicating a long-lasting effect of cannabinoids on responding for heroin. These findings indicate that relapse to heroin after an extended drug-free period is triggered by cannabinoid agonists and that SR 141716A prevents drug-seeking behaviour, suggesting that the use of the cannabinoid antagonist could have some therapeutic benefits in heroin-induced relapse.

Animals↗
PubMed2002

Astroglial in vivo response to cocaine in mouse dentate gyrus: a quantitative and qualitative analysis by confocal microscopy.

Astrocytes have been proved to play a critical role in neuromodulation, neuroprotection, pH maintenance, axon guidance control during development, homeostasis preservation and blood brain barrier maintenance in the CNS (Kimmelberg and Norenberg, 1989). Quantitative changes in the expression of glial fibrillary acidic protein (GFAP), a cytoskeletal intermediate filament protein exclusively expressed in astrocytes (Bignami et al, 1972), have been observed after administration of alcohol (Framke, 1995), morphine (Beitner-Johnson et al., 1993), amphetamine and its derivates (Aguirre et al., 1999), cannabinoids (Suarez et al., 2000), nicotine (Janson and Moller, 1993), caffeine (Marret et al., 1993) and prenatal exposure to cocaine (Clarke et al., 1996; Nassogne et al., 1998). However, the general astrocytic response to drugs of abuse is still far from being defined. In the present study we examined the in vivo astroglial response to cocaine in mouse dentate gyrus, the hippocampus being a common target of neurotoxic agents (Walsh and Emerich, 1988) which has a prominent effect on learning and memory processes (Eichenbaum et al., 1992). Quantitative changes in immunoreactivity of GFAP were investigated 24 h after acute and repeated daily administration of intraperitoneal cocaine (20 mg/kg). Drug-induced morphological alterations and spatial distribution of astrocytes were evaluated by means of confocal microscope. The results show that, compared to control animals, GFAP expression is two-fold enhanced after a single cocaine injection, still significantly higher after seven consecutive daily administrations, but not statistically different after prolonged (14 days) drug treatment. Moreover, morphological and morphometric analyses reveal significant modifications in astrocytic numbers, cell size and shape complexity. These data demonstrate that in mouse dentate gyrus, cocaine exposure differently affects the expression of GFAP and induces strong changes in astrocytes proliferation rate and cell morphology. Taken together, our findings provide the first in vivo quantitative and qualitative evaluation of astrocytic response to several regimens of cocaine in adult animals brain.

Animals↗
PubMed2001

Baclofen antagonises intravenous self-administration of gamma-hydroxybutyric acid in mice.

gamma-Hydroxybutyric acid (GHB) is a widely used recreational drug known to exert positive reinforcing effects in animals and humans. The GABA(B) receptor agonist baclofen has been proved to possess antimotivational effect and to inhibit alcohol, cocaine, heroin and nicotine intake. In the present study we evaluated the effect of baclofen on i.v. self-administration of GHB in drug-naive mice under a fixed-ratio (FR-1) schedule of reinforcement and nose-poking-like response as operandum. Results show that baclofen was able to completely prevent GHB seeking behaviour, decreasing the rate of responding to basal values, without showing any reinforcing properties when made contingent on nose-poking response. Our findings demonstrate that baclofen antagonises GHB i.v. self-administration, supporting an important role for the GABA(B) receptor in reward-related mechanisms underlying addictive behaviour.

Animals↗
PubMed2001

Functional interaction between opioid and cannabinoid receptors in drug self-administration.

The present study was designed to explore the relationship between the cannabinoid and opioid receptors in animal models of opioid-induced reinforcement. The acute administration of SR141716A, a selective central cannabinoid CB1 receptor antagonist, blocked heroin self-administration in rats, as well as morphine-induced place preference and morphine self-administration in mice. Morphine-dependent animals injected with SR141716A exhibited a partial opiate-like withdrawal syndrome that had limited consequences on operant responses for food and induced place aversion. These effects were associated with morphine-induced changes in the expression of CB1 receptor mRNA in specific nuclei of the reward circuit, including dorsal caudate putamen, nucleus accumbens, and septum. Additionally, the opioid antagonist naloxone precipitated a mild cannabinoid-like withdrawal syndrome in cannabinoid-dependent rats and blocked cannabinoid self-administration in mice. Neither SR141716A nor naloxone produced any intrinsic effect on these behavioral models. The present results show the existence of a cross-interaction between opioid and cannabinoid systems in behavioral responses related to addiction and open new strategies for the treatment of opiate dependence.

Animals↗
PubMed2001

Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse.

The rewarding effects of morphine, cocaine, amphetamine and nicotine were evaluated in CB1 receptor knockout mice by means of an intravenous self-administration model. Experiments were carried out on drug-naive animals using a nose-poking response (NPR)-like as operandum. The results of the present study indicate that morphine did not induce intravenous self-administration in mutant CB1 receptor knockout mice, whereas it was significantly self-administered by the corresponding wild type mice. On the contrary, cocaine, amphetamine and nicotine were self-administered to the same extent by both wild type and CB1 receptor knockout mice. These data clearly indicate that the CB1 cannabinoid receptor is essential not only for the expression of cannabinoid reinforcing effects but also for the modulation of morphine rewarding effects. The specificity of such interaction is supported by the finding that contrary to morphine, cocaine, d-amphetamine and nicotine were self-administered by mice at the same extent either in presence or in absence of the CB1 receptor.

Amphetamine↗
PubMed2001

Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats.

RATIONALE: Delta9-tetrahydrocannabinol (Delta9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A. OBJECTIVE: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 microg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. RESULTS: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. CONCLUSION: Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.

Analgesics↗
PubMed2001

Indications for dual-chamber cardioverter defibrillators at implant and at 1 year follow-up: a retrospective analysis in the single-chamber defibrillator era.

AIM: This retrospective four-centre study assessed the current indications for dual-chamber implantable cardioverter defibrillators (ICDs) at implant and during a medium-term follow-up period in a group of patients treated by single-chamber ICD in the pre dual-chamber ICD era. METHODS AND RESULTS: The study population consisted of 153 consecutive patients (127 males, mean age 58 +/- 6 years) treated by single-chamber ICD for ventricular tachycardia and/or ventricular fibrillation. Definite indications for having a dual-chamber ICD included the presence of sinus node dysfunction and of second- or third-degree atrioventricular (AV) block, while possible indications were represented by paroxysmal atrial fibrillation or flutter and first-degree AV block. At implant, dual-chamber ICD would appear definitely indicated in 10.5% of cases, and possibly indicated in an additional 17.5% of cases. During 12 +/- 10 months follow-up, such percentages remained stable (11 and 19.5%, respectively). Inappropriate ICD intervention was documented in five of 13 patients (38%), with episodes of paroxysmal atrial fibrillation or flutter. CONCLUSION: In this non-selected study population, a dual-chamber ICD would have potentially benefited approximately 30% of the patients. During medium-term follow-up, there was no progression towards increasing dual-chamber ICD indications. The 15% cumulative incidence of paroxysmal atrial tachyarrhythmias justifies the activation of dedicated detection algorithms.

Adult↗
PubMed2001

Evidence of pituitary adenylate cyclase activating polypeptide (PACAP) in pancreatic islet cells by confocal microscopy.

Several studies have shown that pituitary adenylate cyclase activating polypeptide (PACAP) stimulates at very low concentration insulin release from pancreatic beta cells. In addition, PACAP has been evidenced in pancreatic nervous fibers surrounding the islets, the core of the islet, and the capillaries. The aim of the present study was to demonstrate internalization of PACAP in pancreatic islet cells. Pancreatic islets were obtained from Wistar rat pancreata by modified Lacy's isolation method. The isolated islets were incubated in the presence of Fluo-PACAP 27, a fluorescent ligand specific for PACAP receptors. At the end of incubation the islets were fixed in paraformaldehyde and then observed by confocal microscope. Fluo-PACAP 27 was internalized into pancreatic islet cells, and this process was time- and temperature-dependent (37 degrees C). The fluorescent molecules converged toward the nucleus where an intense fluorescence was evidenced after 60 minutes. Incubation with phenyl arsine oxide as well as with PACAP 6-38, a receptor antagonist, prevented the internalization process. Further studies are required to explain the internalization process of PACAP 27 into the nucleus of pancreatic islet cells.

Animals↗
PubMed2001

[Effectiveness and side effects of the treatment with propafenone and flecainide for recent-onset atrial fibrillation].

BACKGROUND: The authors report their experience in recent-onset atrial fibrillation treated with intravenous flecainide and propafenone, in comparison with the placebo group. METHODS: We randomized 352 (138 in the flecainide group, 164 in the propafenone group and 50 in the control group) consecutive patients (167 males, 185 females, mean age 59 +/- 12 years) with recent-onset atrial fibrillation. The electrocardiogram of all patients was monitored for at least 24 hours. RESULTS: The restoration of sinus rhythm occurred in 72.5, 80.4, 86.2 and 89.8% of patients in the flecainide group; in 54.3, 68.3, 75 and 92.1% in the propafenone group; in 22.2, 27.8, 35.2 and 46.3% in the control group, at 1, 3, 6 and 24 hours respectively. The occurrence of side effects was the same in all treatment groups, and occurred in about 10% of patients in the flecainide and propafenone groups, and in 4% in the control group. In our study population the treatment of recent-onset atrial fibrillation with flecainide was faster in converting the arrhythmia to sinus rhythm (p < 0.005 at 1 hour, p < 0.05 at 3 hours, p = 0.05 at 6 hours). However within 24 hours the efficacy of either flecainide or propafenone was the same (p = NS at 24 hours). CONCLUSIONS: Side effects were similar in both treatment groups. In particular malignant arrhythmias did not occur in the treatment groups and in the control group.

Adult↗
PubMed2000

The cyclo-oxygenase inhibitor nimesulide induces conditioned place preference in rats.

Two cyclo-oxygenase inhibitors, indomethacin and nimesulide, have been shown to potentiate morphine-induced stimulation of meso-accumbens dopamine neurons. In this study, an unbiased conditioned place preference procedure was used to evaluate whether nimesulide produces motivational effect after systemic administration in rats. These results show that nimesulide, at doses 0.1, 0.5 and 1 mg/kg, even lower than those usually applied for inflammatory conditions, induces conditioned place preference in rats, suggesting that it might possess rewarding properties in humans.

Animals↗
PubMed2000

Gamma-hydroxybutyric acid: an evaluation of its rewarding properties in rats and mice.

Gamma-hydroxybutyric acid, an endogenous compound present in mammalian brain and supposed to be a neurotransmitter or neuromodulator, has been shown to affect several aspects of dependence from some drugs of abuse. It has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. The aim of this study was to investigate whether gamma-hydroxybutyric acid possesses rewarding properties by means of conditioned place preference and intravenous self-administration paradigms. In the present study, gamma-hydroxybutyric acid induced conditioned place preference in rats, was intravenously self-administered by drug-naive mice, and altered cocaine intravenous self-administration in rats. Although to date the physiological role of this compound still remains unclear, there is no doubt that gamma-hydroxybutyric acid, in addition to its proved effect on alcohol and opiate dependence, possesses reinforcing properties of its own and may interfere with the neurochemical events in the rewarding effects produced by psychostimulant drugs. Our investigation points out the abuse liability of this drug, suggesting the use of particular precaution in handling gamma-hydroxybutyric acid as a clinically useful drug.

Animals↗
PubMed2000

[Assessment of plasma lipid profile in acute coronary syndromes. The use of fibrinolytics and heparin do not affect it significantly].

BACKGROUND: Neurohormonal and metabolic responses to acute ischemic events associated with thrombolysis and heparin induce substantial changes in the lipid profile (acute phase response). The aim of this study was to assess changes in total cholesterol and triglycerides in patients with acute coronary syndrome, admitted to our Intensive Coronary Care Unit (ICCU). METHODS: The study included 1051 consecutive patients, 316 with unstable angina, 583 with Q wave acute myocardial infarction (AMI) and 152 with non-Q wave AMI. Total cholesterol and triglycerides were measured in all patients at time 0 (admission), at time 1 (the morning following admission), at time 2 (the morning after discontinuation of heparin treatment). RESULTS: The mean value of total cholesterol at admission was 235, 210 and 197 mg% at admission, time 1 and time 2, respectively. Triglyceride levels were 234, 178 and 189 mg%, respectively. In the subgroup of thrombolized AMI the reduction in total cholesterol at time 1 and time 2 resulted similar in comparison with non-thrombolized AMI (p = NS). The decrease in triglycerides showed a similar pattern in the different subgroups. Comparison was also done according to sex, age, and complications. CONCLUSIONS: These data confirm that mean total cholesterol and triglycerides at admission are sharply higher than values considered normal in the literature. Within 24 hours of admission there is a 10.7% drop in total cholesterol which increases to 16.2% after a few days (mean 3.4 days). Total cholesterol determination upon admission in patients with acute coronary syndromes is necessary in order to know the true concomitant lipid profile during the precipitating ischemic events. The decision of initiating early therapy with statins would then appear more justified.

Aged↗
PubMed1999

CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats.

The effect of the CB1 cannabinoid receptor agonist WIN 55,212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55,212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB1 receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55,212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB1 cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine.

Animals↗
PubMed1998

Gamma-hydroxybutyric acid decreases intravenous cocaine self-administration in rats.

Gamma-hydroxybutyric acid (GHB) is an endogenous compound present in mammalian brain suggested as a putative neurotransmitter, which has been shown to affect several aspects of dependence from various classes of drugs of abuse. In the present study, two sets of experiments were performed to investigate the effects of acute pretreatment with GHB on intravenous cocaine self-administration in rats. In the first experiment GHB was administered intragastrically at the doses of 175, 350, and 700 mg/kg to Long-Evans rats trained to self-administer cocaine using nose-poke as operandum. In the second experiment, GHB was administered intraperitoneally at the doses of 100, 200, and 400 mg/kg to Wistar rats trained to self-administer cocaine intravenously using lever-pressing as operandum. In both experiments acute pretreatment with GHB significantly and dose dependently reduced cocaine self-administration. The effectiveness of GHB was similar in both experiments, indicating that the effect of GHB on cocaine self-administration is independent of animal strain. route of administration, and type of operant response required. These results indicate that GHB reduces cocaine-seeking behavior in rats, modulating the acute reinforcing effect of cocaine. The clinical effectiveness of GHB in dependence from various classes of abused drugs warrants further studies to evaluate the possibility that GHB might represent a useful therapeutic agent for cocaine addiction in humans.

Anesthetics, Intravenous↗
PubMed1998

Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice.

Marijuana is one of the most widely used illicit recreational drugs. However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased. The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB1 receptors.

Analgesics↗
PubMed1998

Intravenous self-administration of gamma-hydroxybutyric acid in drug-naive mice.

The reinforcing effects of gamma-hydroxybutyric acid (GHB) were studied by means of intravenous self-administration in drug-naive mice. GHB self-administration was concentration-dependent (0.01-0.5 mg/kg/inj.) according to a bell-shaped curve. Pretreatment with the specific GHB receptor antagonist NCS-382 at a dose of 12.5 mg/kg i.p. completely antagonized the reinforcing effects of GHB. These data suggest that GHB is able to induce reinforcing effects in mice and support the hypothesis of an abuse liability of this drug.

Animals↗
PubMed1998

The increased frequency of hypercholesterolemia in southern Italy is induced only by changing diet quality?

BACKGROUND: The purpose of this paper is to evaluate cholesterolemia and triglyceridemia in relation to BMI, alimentary habits and physical activity. DESIGN: We compare our epidemiological data with those obtained in other studies previously carried out in Campania: "CNR-ATS-RF2-OB43". SETTING: Campania (Italy). RESULTS: Data show an increase of these risk factors in Southern Italy from 1978 to 1989. In males, between 20 and 59 years the prevalence of hypercholesterolemia increases from 15.9% in 1978-1979 (CNR-RF2) to 17.8% in 1983-1984 (ATS-OB43), and 20.6% in our own data (1988-1990). The pattern is similar for females: 14.4% (1978-79), 16.7% (1983-1984), and 18.6% (1988-1990). In males hypertriglyceridemia increases from 17% in 1978-1979, to 21.3% in 1983-1984 and 36.2% in 1988-1990. In females from 9.8% to 12.4% and 18% respectively. CONCLUSIONS: This reality can be explained through the gradual changing of alimentary habits (high consumption of saturated fats and very little intake of vegetal fibres) and by reduced physical activity that contributes to the progressive BMI increase.

Body Mass Index↗