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Biomedical subjects

L Pulvirenti

Publications and source records attributed to L Pulvirenti.

At least 19 recordsLinked to original sources

The effect of gender on planning: An fMRI study using the Tower of London task.

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.

Adult↗

A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule.

A recently characterized class of compounds, dopamine partial agonists, have been suggested as potential therapeutic candidates for pharmacological intervention in psychostimulant addiction. These drugs bind to dopamine receptors with high affinity and low intrinsic activity and are thought to behave as functional antagonists in conditions of high dopaminergic tone, and as agonists in conditions of low receptor occupancy by dopamine. The aim of the present study was to characterize the effects of terguride, a partial dopamine agonist at the D2 receptor subtype, on intravenous self-administration of amphetamine in a progressive ratio schedule and to compare it with the effects produced by the dopamine D2 antagonist eticlopride and the dopamine D2 full agonist quinpirole. Terguride at the doses of 0.2 and 0.4 mg/kg i.p. significantly decreased the maximum number of responses delivered for a single injection of amphetamine ("breaking point"), an effect similar to that produced by the antagonist eticlopride (0.01-0.1 mg/kg s.c.). In contrast, administration of quinpirole (0.1-1 mg/kg s.c.) did not significantly modify the breaking point for amphetamine responding. Also, terguride dose-dependently increased responding for amphetamine self-administration on a continuous reinforcement schedule. These data further confirm the effects of terguride on psychostimulant self-administration and indicate that under these conditions partial dopamine agonists act as functional dopamine receptor antagonists.

Amphetamine↗

Dopamine partial agonist reverses amphetamine withdrawal in rats.

Decreased motivation to work for a natural reward is a sign of amphetamine withdrawal and is thought to be associated with hypofunction of the mesolimbic dopamine system. During withdrawal from repeated amphetamine administration, rats showed reduced responding for a sweet solution in a progressive ratio schedule. Repeated systemic treatment with terguride (0.2 and 0.4 mg/kg, i.p.) twice daily during the first four days of amphetamine withdrawal reversed the decrease in responding for the sweet solution. These results suggest that dopamine partial agonists, possibly due to their agonistic-like actions under these conditions, are a potential therapeutic approach for the acute withdrawal stage of the amphetamine addition cycle.

Amphetamine↗

Drug dependence as a disorder of neural plasticity: focus on dopamine and glutamate.

Drug addiction, as a disease, has grown to reach the level of a social illness. Psychostimulants, opiates, alcohol, nicotine and cannabis abuse affects millions worldwide and virtually all classes of modern society. In spite of the enormous proportions of its spread, intimate neurobiological mechanisms leading to distintictive features of this pathological status, such as craving for the abused substance and loss of control over intake, remain largely obscure and pharmacotherapies sadly unsatisfactory. In the last decade, preclinical and clinical research in this field has made great progress to improve our understanding of the brain mechanisms which form the basis of this illness. The review of recent literature, which represents the focus of the present paper, leads to the emerging consensus that an alteration of physiological mechanisms of neural plasticity within the brain dopamine and glutamate systems may underlie some of the behavioral abnormalities occurring during the dependence cycle. In particular, a reduction of dopamine neuronal activity and glutamate neurotransmission at the level of the ventrotegmental area, after withdrawal from chronic administration of drugs of abuse, may work in concert with alterations in other forebrain areas, such as the nucleus accumbens and the amygdaloid complex. In addition, following prolonged periods of abstinence, even after somatic withdrawal signs have vanished, responsiveness of these systems to drugs of abuse remains abnormal. This suggests that these two neurotransmitters may play a substantial role in the long-lasting, enduring changes typical of the addictive process and may represent ideal targets for pharmacological intervention aimed at normalizing forms of neural plasticity impaired after chronic drug intake.

Animals↗

Cocaine induced T cell proliferation in the rat: role of amygdala dopamine D1 receptors.

The immunomodulatory effects of local administration of cocaine into the amygdala were studied in the rat. Intra-amygdala infusion of cocaine significantly and dose-dependently increased the proliferative response of splenocytes to concanavalin A (Con A). A similar effect on the immune response was also observed in rats, microinfused into the central amygdala with the selective D1 receptor agonist SKF 38393. The increase of the proliferative response of splenocytes to Con A was inhibited by coinfusion within the central amygdala of the dopamine D1 receptor antagonist SCH 23390, together with cocaine, but not by coinfusion of the dopamine D2 receptor antagonist eticlopride. These results suggest that cocaine may produce at least some of its effects on the immune system through the activation of brain dopamine neurotransmission and that the central amygdala may represent a critical structure mediating cocaine-induced T cell proliferation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

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↗

Characterization of the effects of the partial dopamine agonist terguride on cocaine self-administration in the rat.

Dopamine neurotransmission is an important neuropharmacological component of cocaine self-administration in rodents. Terguride is a prototype drug belonging to a recently characterized class of compounds, dopamine partial agonists, which appear to possess a unique pharmacological profile in altering dopamine neurotransmission, where these drugs act as antagonists in conditions of high dopaminergic tone. The aim of the present study was therefore to test the effects of systemic administration of terguride in rats self-administering cocaine intravenously. The different aspects of cocaine self-administration examined after treatment with terguride were (a) the acute reinforcing properties of cocaine in rats exposed to limited-access self-administration of cocaine, (b) a full cocaine dose-effect function, (c) the reinforcing properties of cocaine as measured by a progressive ratio schedule and (d) the ability of terguride to maintain self-administration by itself. Terguride (0.025-0.4 mg/kg i.p.) significantly and dose-dependently reduced the acute reinforcing properties of cocaine as measured by an increase in responding for a single training dose of cocaine and a reduction of the inter-reinforcement interval. In addition, terguride (0.2-0.4 mg/kg) shifted the entire cocaine dose-effect function to the right, thus showing an antagonism of the reinforcing properties of cocaine independent of response rate. Moreover, in rats trained to self-administer cocaine on a progressive ratio schedule, terguride reduced the maximum fixed ratio ("breaking point") for cocaine reinforcement, also suggesting a decrease in the reinforcing properties of cocaine. Finally, in rats trained to self-administer cocaine terguride did not substitute for cocaine, thus indicating that terguride does not maintain intravenous self-administration by itself.

Animals↗

Dextromethorphan reduces intravenous cocaine self-administration in the rat.

Dextromethorphan is a widely used antitussive agent with non-competitive antagonistic effects at the excitatory amino acid receptors of the NMDA type. Since excitatory amino acid neurotransmission has been implicated in cocaine dependence, the aim of the present study was to evaluate the effects of acute systemic administration of dextromethorphan in rats trained to self-administer cocaine intravenously. The experiments were designed to evaluate the effects of dextromethorphan on responding for cocaine and cocaine reward magnitude. The hypothesis was that dextromethorphan could attenuate specific aspects of cocaine-seeking behavior thus providing a preclinical rationale for its clinical use. The results reported reveal that acute pretreatment with dextromethorphan (10-50 mg/kg i.p.) significantly reduced cocaine self-administration in rats self-administering the drug intravenously in a simple continuous reinforcement schedule. In addition, acute pretreatment with an effective dose of dextromethorphan (25 mg/kg) decreased cocaine self-administration in rats tested at various doses of cocaine (0.12-0.5 mg/injection). Finally, dextromethorphan (25 mg/kg) also reduced the absolute reward magnitude of cocaine as measured by responding for cocaine in a progressive ratio schedule. These results encourage further experimental and clinical studies to evaluate the potential use of dextromethorphan during various phases of the natural history of cocaine dependence in humans.

Animals↗

Dopamine partial receptor agonists reduce ethanol intake in the rat.

Dopamine neurotransmission is an important neuropharmacological component of ethanol reinforcement in rodents. A recently characterized class of compounds, dopamine partial receptor agonists, appears to possess a unique pharmacological profile on dopamine neurotransmission. The aim of the present study was to test the effects of systemic administration of terguride and SDZ 208-911 (N-[(8 alpha)-2,6-dimethylergoline-8-yl]-2,2-diethylpropanamide), two prototype dopamine partial receptor agonists, in free-feeding, non-deprived rats trained to drink ethanol (10% w/v) and water in 'free-choice' limited access conditions. Both acute and chronic administration of terguride and SDZ 208-911 significantly reduced ethanol intake while water intake was not significantly affected, thus ruling out possible non-specific effects of these drugs on fluid intake. These results suggest that dopamine partial receptor agonists reduce the reinforcing properties of ethanol in the rat, an effect similar to that previously observed with cocaine. Therefore, the pharmacological profile of dopamine partial receptor agonists and their effects in animal models of dependence provide preclinical support to the hypothesis that these compounds may represent a novel pharmacological strategy for intervention in various forms of drug addiction.

Alcohol Drinking↗

Inhibition of nitric oxide synthesis reduces intravenous cocaine self-administration in the rat.

The effects of a blockade of nitric oxide synthesis were studied in rats trained to self-administer cocaine intravenously. Pretreatment with Ng-nitro-1-arginine methyl ester (l-NAME; 10-50 mg/kg, intraperitoneally, twice daily for 4 days), significantly and dose-dependently suppressed the maintenance of intravenous cocaine self-administration and the absolute reward magnitude of cocaine. These results suggest that nitric oxide may play a role in cocaine abuse and dependence.

Animals↗

[Prevalence of hepatitis C virus infection in different groups of selected populations].

The objective of this study to determine the prevalence of hepatitis C virus at Caltagirone (CT) among blood donors, health care workers, drug users, hemodialysis patients and thalassaemics. The identification of risk factors for HCV infection and liver function in HCV correlate hepatitis. Anti-hepatitis C virus antibodies were detected in 0.64% of blood donors, in 68.44% of drug users, in 58.55% hemodialysis patients and in 67.50% of thalassaemics. Drug abuse, haemodialysis, blood transfusions are the major risk factors for hepatitis C.

English Abstract↗

Cocaine abuse and dependence.

Western countries experienced a widespread cocaine epidemic during the 1980s, and the number of frequent users has not declined in this decade. A key factor in the development of this epidemic has been the introduction of "crack," an affordable form of cocaine that appears to be more addicting than the powder. Epidemiologic studies indicate a high incidence of polysubstance abuse among cocaine abusers and probable gender differences in patterns of abuse and response to treatment. An abstinence syndrome has been documented in outpatients after the acute cessation of cocaine; the symptoms perhaps depend on the presence of cues to evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine is a psychostimulant drug that possesses euphorigenic and reinforcing properties. The fact that various animal species self-administer cocaine through the intravenous route provides a reliable animal model for the study of the molecular mechanism of cocaine action and for the characterization of the anatomical substrates responsible for the rewarding properties of the drug. A multisynaptic, allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to play an important role. This pathway may also be part of the neuronal substrates that mediate the reinforcing properties of other classes of abused drugs and, perhaps, motivated behavior in general. Because of this potent reinforcing nature of cocaine in humans, the problem of designing effective therapy for its addiction has not been simply solved. Clinical treatments, guided by animal studies and designed for specific attack of symptoms of the abstinence syndrome, craving and anhedonia, have been tested. To date, only a few agents have proved effective in controlled trials (amantadine, bromocriptine, carbamazepine, and desipramine) and these have limitations of side effects or delayed onset of action. Agents that interact with specific subcomponents of the dopamine system or its connections offer promise for the development of successful agents to treat cocaine abuse and craving in humans.

Animals↗

Dopamine D1 receptors in the amygdala enhance the immune response in the rat.

Indirect evidence suggests that dopamine within the brain may participate in the regulation of immune responses in both man and rodents. The aim of the present study was to investigate the possible role played by the specific dopamine D1 receptor subtype within the central amygdala in the modulation of immunity. Mitogen responsiveness of splenocytes and NK cell activity were measured in rats following local microinfusion of SKF 38393, a specific dopamine D1 receptor agonist. Microinfusion of SKF 38393 (100 nmol) within the central amygdala increased the proliferative response of splenocytes to Con A, whereas it did not modify the proliferative response of splenocytes to LPS or NK cell activity. The effects of SKF 38393 were prevented by prior systemic administration of SCH 23390 (0.3 mg/kg ip), a specific D1 receptor antagonist. These results indicate that activation of dopamine D1 receptors within the central amygdala induced selective stimulation of mitogen responsiveness of splenocytes and suggest that specific activation of dopamine neurotransmission within selected areas of the limbic system may produce immunoenhancing effects. These findings further confirm the immunomodulatory role played by dopaminergic mechanisms in the brain.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Modulation of locomotor activity by NMDA receptors in the nucleus accumbens core and shell regions of the rat.

Two subdivisions of the nucleus accumbens (NAC), the core and the shell, have been recently identified on the basis of immunohistochemical differences and neural connections. A major neural input to the NAC is provided by glutamatergic afferents of allocortical origin and there is evidence that glutamate can modulate psychomotor activation and drug reinforcement. This study was undertaken to explore whether selective pharmacological blockade of NMDA neurotransmission within the core and the shell region affected differentially spontaneous and cocaine-induced locomotor activity. We report that intra-NAC microinfusion of aminophosphonovaleric acid (AP-5) (0.75-3.0 micrograms/side, 1.5-6.0 micrograms total dose) within the core but not the shell region reduced cocaine-induced locomotion in a dose-dependent manner. In contrast, microinfusion of the same doses of AP-5 within the shell region caused a dose-dependent increase of spontaneous locomotion, while microinfusion within the core region was ineffective. These results indicate that blockade of NMDA receptors in the core and the shell of the NAC elicited different effects on spontaneous and cocaine-induced locomotion. This suggests that these substructures may subserve different functions within the integrated output of the NAC, functions that may vary according to the state of arousal.

2-Amino-5-phosphonovalerate↗

The effects of lisuride on mood and sleep during acute withdrawal in stimulant abusers: a preliminary report.

Psychostimulant abusers often experience anhedonia, depression, fatigue, craving, and hypersomnia and increased propensity for rapid eye movement (REM) sleep during periods of acute and subacute withdrawal from cocaine and amphetamine. These signs and symptoms may reflect a state of relative functional dopamine depletion in the brain during abstinence. Lisuride, which has dopaminergic agonist effects, has been reported to reduce signs of psychostimulant withdrawal in rodent models of stimulant abuse. These observations prompted us to test the effects of oral administration of lisuride for 3 weeks (up to 4.0 mg daily) on mood and craving ratings in a double-blind, parallel design, controlled study in hospitalized stimulant abusers during acute withdrawal from cocaine or amphetamine. Although administration of lisuride significantly prolonged REM latency and reduced REM time, amelioration of other signs of withdrawal was not significantly greater in lisuride as compared with placebo treated patients. Self-rated craving ratings, however, were low in both groups throughout the hospital stay. Further studies, perhaps in patients with more severe symptoms during withdrawal, are needed to fully test the efficacy of lisuride in the treatment of stimulant withdrawal.

Administration, Oral↗

SDZ 208-911, an amino-ergoline with partial dopamine agonist properties, dose dependently increases cocaine self-administration in the rat.

Brain dopamine neurotransmission appears to be an important component of the neural pathways involved in the maintenance of intravenous (IV) cocaine self-administration in rats. The effects of a novel partial dopamine agonist, SDZ 208-911, on intravenous cocaine self-administration in rats was studied. SDZ 208-911 at a dose range of 0.025-1.6 mg/kg SC dose-dependently increased the number of lever presses and drug intake in rats exposed to limited (3-h) daily access to cocaine on a continuous reinforcement schedule (0.75 mg/kg per injection). This behavioral profile is similar to that observed following administration of dopamine antagonist drugs and has been hypothesized to reflect a compensatory increase in drug intake due to a reduction of the reinforcing efficacy of the drug, probably because of functional antagonism at the receptor site. These results suggest that dopamine partial agonists may act as functional dopamine antagonists in the face of pharmacologically induced activation of brain dopamine function.

Animals↗

Lisuride reduces intravenous cocaine self-administration in rats.

The maintenance of intravenous (i.v.) cocaine self-administration appears to depend upon activation of dopamine terminals within mesocorticolimbic areas. Since the nonaddictive ergot derivative lisuride is a direct dopamine receptor agonist, the present study was designed to investigate whether administration of lisuride to rats trained to lever-press for IV self-administration of cocaine could affect the intake of cocaine. IP administration of several doses of lisuride reduced, in a dose-dependent manner, cocaine self-administration. In a control experiment, lisuride did not increase the psychomotor-activating properties of cocaine as measured by locomotor activity, suggesting that lisuride did not simply potentiate the activating effects of cocaine. The present results show that lisuride reduced IV cocaine self-administration in rats; the possibility of a new therapeutic approach to the treatment of cocaine abuse in humans using lisuride may therefore deserve clinical attention.

Animals↗