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L Pulvirenti

Publications and source records attributed to L Pulvirenti.

At least 37 records · Page 2Linked to original sources
PubMed1994

Dopamine receptor agonists, partial agonists and psychostimulant addiction.

Despite the epidemic growth of psychostimulant addiction over the past years, few pharmacological means of intervention are available to date for clinical treatment. This is of importance since the withdrawal syndrome that follows abstinence from drugs such as cocaine and the amphetamines is characterized, among other symptoms, by intense craving for the abused drug, and this is considered a critical factor leading into relapse of drug use. In this article, Luigi Pulvirenti and George Koob focus on the modulatory role shown by drugs acting at the dopamine receptor on the various phases of psychostimulant dependence in preclinical models and in human studies, and suggest that a class of compounds with partial agonist properties at the dopamine receptor may have therapeutic potential.

Amphetamines↗
PubMed1994

Role for the mesocortical dopamine system in the motivating effects of cocaine.

The search for a neurobiological substrate for the stimulant and reinforcing properties of cocaine has focused for some time on a particular part of the forebrain, the mesocorticolimbic dopamine (DA) system. This mesocorticolimbic DA system innervates the region of the nucleus accumbens (NACC) (ventral striatum) in the anterior part of the basal forebrain and appears to play a critical role in mediating the acute reinforcing effects of cocaine and amphetamine. This chapter reviews the role of mesocorticolimbic DA in the reinforcing properties of psychomotor stimulants as measured by intravenous (IV) drug self-administration in rats. In addition, the primary neuropharmacological mechanism for cocaine reinforcement provides a rich substrate for studying nondopaminergic modulation of the reinforcing actions of cocaine.

Animals↗
PubMed1993

Lisuride reduces psychomotor retardation during withdrawal from chronic intravenous amphetamine self-administration in rats.

Withdrawal from chronic use of psychostimulant drugs in humans induces a clinical syndrome characterized by fatigue, psychomotor depression, anhedonia, and disturbances of sleep. Spontaneous locomotor activity and catalepsy were assessed in rats during withdrawal from a schedule of intravenous self-administration of high doses of amphetamine. At 2 and 4 days after cessation of amphetamine self-administration, rats showed a state of psychomotor retardation as measured by reduction of locomotor activity and increased catalepsy. In search of a possible pharmacologic means of intervention for such behavioral changes, the effect of repeated treatment with the nonaddictive ergot derivative lisuride during the withdrawal phase was evaluated. At a dose devoid of any effects on locomotor activity, lisuride completely prevented the reduction in locomotor activity and the increase in catalepsy produced by amphetamine withdrawal. These results suggest the need for further studies on lisuride as a possible novel treatment during withdrawal from psychostimulant drugs in humans.

Amphetamine↗
PubMed1992

NMDA receptors in the nucleus accumbens modulate intravenous cocaine but not heroin self-administration in the rat.

The role of endogenous glutamate neurotransmission within the nucleus accumbens in the modulation of intravenous (i.v.) cocaine and heroin self-administration in rats was analyzed. APV (2-amino-5-phosphonovaleric acid), a blocker of glutamate receptors of the N-methyl-D-aspartate (NMDA) type, was microinfused within the nucleus accumbens of the ventral striatum of rats trained to lever press for i.v. cocaine or heroin self-administration. APV, at the dose of 1.5 and 3.0 micrograms/side, reduced the rewarding value of cocaine while it left heroin self-administration unaffected. These results suggest that integrity of NMDA receptor function within the nucleus accumbens may be of importance for the maintenance of i.v. cocaine, but not heroin self-administration in rats.

2-Amino-5-phosphonovalerate↗
PubMed1992

Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens.

The purpose of this study was to assess the role of endogenous dopamine and glutamate systems within the nucleus accumbens in modulating responses for oral ethanol reinforcements (10% w/v) in a free-choice operant task. Pretreatment with both systemic (100 micrograms/kg) and intra-nucleus accumbens microinjection of fluphenazine (2 and 4 micrograms), a dopamine receptor antagonist, significantly decreased responding for ethanol, without significantly affecting responses for water. Ethanol self-administration was also attenuated by microinjection into the nucleus accumbens of 2-amino-5-phosphopentanoic acid (AP-5, 3 and 6 micrograms), a competitive NMDA receptor antagonist. These results suggest that dopamine and glutamate neurotransmission in the nucleus accumbens may regulate ethanol self-administration and its reinforcing effects.

2-Amino-5-phosphonovalerate↗
PubMed1992

Effects of thyrotropin-releasing hormone, oxytocin, and prolactin on thiopenthal-induced narcosis in rats.

Neuropeptides that may induce behavioral activation--thyrotropin-releasing hormone (TRH), oxytocin (OXY), and prolactin (PRL)--were tested on thiopenthal-induced narcosis after IV administration in male rats. TRH caused a significant shortening of sleeping time at the doses of 3 and 5 mg/kg, but did not change this parameter at lower doses. Oxytocin was effective at all doses tested (200, 300, and 400 micrograms/kg). Prolactin also shortened sleeping time at the doses of 0.2 and 1 mg/kg administered IV, slightly increasing it at the dose of 5 mg/kg. These results indicate that various neuropeptides are capable of reducing the duration of thiopenthal-induced sleep in rats.

Animals↗
PubMed1991

Nucleus accumbens NMDA antagonist decreases locomotor activity produced by cocaine, heroin or accumbens dopamine, but not caffeine.

Glutamatergic afferents to the nucleus accumbens (NAC) have been suggested to modulate psychostimulant-induced locomotor activation. The purpose of this study was 1) to determine the importance of nucleus accumbens N-methyl-D-aspartate (NMDA) glutamate receptors in the control of psychostimulant-induced locomotion, 2) to determine whether NMDA receptor modulation of psychostimulant-induced locomotion occurs presynaptic to or postsynaptic to NAC dopamine terminals, and 3) to determine whether NMDA receptors also modulate opiate- and caffeine-induced locomotor activation. For this purpose, rats treated with cocaine (10 mg/kg IP), dopamine (20 micrograms directly into the NAC), heroin (0.5 mg/kg SC), or caffeine (10 mg/kg SC) were challenged with intra-NAC microinfusion of 2-amino-5-phosphonovaleric acid (APV), a selective NMDA receptor antagonist. APV reduced locomotor activation induced by cocaine, heroin and intra-NAC dopamine, but not caffeine. These results suggest that NAC glutamate modulates psychomotor stimulation at the level of the NAC through an interaction with the integrated output of this region.

2-Amino-5-phosphonovalerate↗
PubMed1991

Endocrine, immune, and neurochemical changes in rats during withdrawal from chronic amphetamine intoxication.

In humans who chronically abuse amphetamine (AMPH), sudden abstinence often precipitates an organic mood disorder that mimics many symptoms of major depression. We report that AMPH exposure and withdrawal in rats modifies hypothalamic-pituitary-adrenal axis endocrine responses, peripheral immune functions, and regional brain catecholamine levels. Compared to vehicle-treated animals, rats treated with AMPH for 10 days exhibit significantly decreased physostigmine-induced release of adrenocorticotropin hormone (ACTH). During AMPH withdrawal, these animals show a loss of the normal correlation between levels of plasma ACTH and corticosterone. Chronic AMPH treatment in rats causes a significant increase in natural killer cell activity. Brain dopamine levels in these animals are decreased in the caudate nucleus but are increased in the nucleus accumbens. AMPH withdrawal in rats may be a useful model for studying the physiologic and neural substrates of human AMPH withdrawal states.

Adrenocorticotropic Hormone↗
PubMed1990

Amphetamine disruption of prepulse inhibition of acoustic startle is reversed by depletion of mesolimbic dopamine.

Previous studies have demonstrated that dopamine (DA) agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats; other reports suggest that this stimulant-induced disruption of PPI may reflect drug-induced increases in ASR amplitude rather than changes in sensorimotor gating. In the current study, 6-hydroxydopamine lesions that depleted dopamine from the nucleus accumbens, olfactory tubercles and anterior striatum reversed the disruption of PPI caused by amphetamine (AMPH), but did not disrupt AMPH potentiation of ASR baseline. These findings strongly suggest that increased mesolimbic DA activity is one substrate of the AMPH-induced disruption of PPI; in contrast, AMPH potentiation of baseline startle amplitude may be independent of mesolimbic DA activation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effects of TRH and prolactin in the behavioral despair (swim) model of depression in rats.

The neuropeptides thyrotropin releasing hormone (TRH) and prolactin (PRL), which affect various behaviors in animals, showed "antidepressant" properties in an experimental model of depression. Subcutaneous administration of TRH reduced the total immobility time of rats tested in the despair (constrained swim) test and potentiated the anti-immobility effect of intraperitoneally administered desimipramine (DMI). This effect was not mimicked by the peripheral injection of TSH, T3 or T4. Hyperprolactinemia induced by pituitary homografts under the kidney capsule and the intracerebroventricular injection of PRL also potentiated the DMI-induced reduction of total immobility time of rats in the despair test and exerted "antidepressant" effects in aged rats.

Aging↗
PubMed1989

Microinjection of a glutamate antagonist into the nucleus accumbens reduces psychostimulant locomotion in rats.

In order to study a possible modulatory effect of glutamatergic afferents to the nucleus accumbens (NAC) on psychostimulant-induced locomotion, L-glutamic acid diethyl ester (GDEE), a glutamate antagonist, was injected in the NAC of rats acutely treated with cocaine, amphetamine or caffeine. GDEE at the doses of 5, 10, and 20 micrograms/side significantly reduced locomotion induced by cocaine (20 mg/kg, i.p.). Amphetamine-induced hyperactivity was also reduced by GDEE, whereas caffeine-induced hyperactivity was not significantly decreased by GDEE. This suggests that glutamatergic afferents to the NAC modulate the effects of psychostimulants and also dopamine function in the mesolimbic system.

Amphetamine↗
PubMed1988

Blockade of brain dopamine receptors antagonizes the anti-immobility effect of MIF-1 and Tyr-MIF-1 in rats.

Previous studies have shown effects of MIF-1 (prolyl-leucyl-glycinamide) and Tyr-MIF-1 (tyrosyl-prolyl-leucyl-glycinamide) in animal models of depression and also effects on dopaminergic function. These observations prompted us to examine whether the effects of the two peptides in the behavioral 'despair' test were modulated by dopamine antagonists. MIF-1 and Tyr-MIF-1, at the small dose of 0.01 mg/kg i.p. (24, 5 and 1 h before the test), produced a significant anti-immobility effect. This effect was antagonized by a single injection of either haloperidol or sulpiride, two dopamine receptor blockers. The same low dose of the tricyclic antidepressant desipramine was without significant effect in this test. The results indicate that Tyr-MIF-1, like MIF-1, is active in the behavioral despair test for antidepressants and that at least some of the CNS actions of these peptides are mediated by dopamine receptors.

Animals↗
PubMed1988

Naloxone, but not Tyr-MIF-1, reduces volitional ethanol drinking in rats: correlation with degree of spontaneous preference.

The possible relationship between the actions of ethanol and opiates led us to examine the effect of opiate antagonists on ethanol intake in rats with a free choice of water. Naloxone (NAL) significantly reduced intake of ethanol. This effect was much greater in "high-preferring" (ethanol/total fluid intake greater than 60%) than in "low-preferring" (ethanol/total fluid intake less than 30%) rats. Furthermore, a correlation was found between the degree of spontaneous preference (ethanol/total fluid intake ratio) and the reduction of ethanol drinking by NAL. Sensitivity to NAL increased with increased preference for ethanol. Neither Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) nor MIF-1 (Pro-Leu-Gly-NH2) caused a significant modification of ethanol intake. This study shows that NAL can reduce volitional ethanol intake in rats and provides further evidence that Tyr-MIF-1 does not always act like NAL.

Alcohol Drinking↗
PubMed1986

Antagonism by dopamine, but not noradrenaline receptor blockers of the anti-immobility activity of desipramine after different treatment schedules in the rat.

The effect of antidopaminergic and antiadrenergic agents on the anti-immobility activity of desipramine after different schedules of treatment was studied in rats. 0.5 mg/kg i.p. haloperidol and 100 mg/kg i.p. sulpiride antagonized the anti-immobility effect of three injections of 10 mg/kg desipramine. Similar results were obtained after 7 or 21 daily doses of 10 mg/kg desipramine. Neither 5 mg/kg i.p. propranolol nor 3 mg/kg s.c. prazosin had any effect on desipramine after the various treatment schedules. It is suggested that DA mechanisms are involved in the anti-immobility effect of repeated desipramine in the rat. A possible role of beta-adrenergic receptors in the development of this effect is discussed.

Animals↗
PubMed1986

Chronic treatment with iprindole reduces immobility of rats in the behavioural 'despair' test by activating dopaminergic mechanisms in the brain.

Iprindole, 10 mg kg-1 i.p., once daily for 21 days, enhanced the metabolism of dopamine in the frontal cortex and striatum of rats with no effect in the nucleus accumbens 1 h after the last injection. Noradrenaline metabolism in the brainstem and telencephalon was also increased in these conditions. No effect on dopamine or noradrenaline metabolism was seen 24 h after the last injection. The same repeated treatment schedule with iprindole markedly reduced the immobility of rats in the behavioural 'despair' test 1 h after the last injection and the effect was prevented by 0.5 mg kg-1 i.p. haloperidol and 100 mg kg-1 i.p. sulpiride but not by 3 mg kg-1 s.c. prazosin or 5 mg kg-1 i.p. (+/-)-propranolol. The data show that enhanced metabolism of brain dopamine and noradrenaline is associated with the presence of iprindole during repeated treatment and the effect on dopamine mechanism is important in iprindole's ability to reduce rats' immobility in the behavioural 'despair' test.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Evidence of dopamine involvement in the effect of repeated treatment with various antidepressants in the behavioural 'despair' test in rats.

Daily treatment for 7 days with 5 mg/kg nomifensine, 20 mg/kg amineptine, 10 mg/kg mianserin or 20 mg/kg iprindole reduced the immobility time in the behavioural 'despair' test in rats. No stimulation of motor activity was found with any of the drugs, and iprindole and mianserin actually reduced the activity of rats in an open field. The anti-immobility effect of the various antidepressants was significantly counteracted by 0.5 mg/kg haloperidol or 100 mg/kg sulpiride. These doses of neuroleptics alone did not significantly modify the immobility time of rats not treated with the antidepressant compounds. As previously found for desipramine and amitriptyline, the data suggest that dopamine is involved in the anti-immobility effect in rats of repeated treatment with nomifensine, amineptine, mianserin and iprindole.

Animals↗