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P Devoto

Publications and source records attributed to P Devoto.

At least 19 recordsLinked to original sources
PubMed2001

Lead intoxication during intrauterine life and lactation but not during adulthood reduces nucleus accumbens dopamine release as studied by brain microdialysis.

Environmentally relevant levels of lead (Pb) have been demonstrated to have a neurotoxic action, especially on children. In this study, Long-Evans rats were continuously exposed to Pb acetate in drinking water from early gestational days (2-6) or from 28 days of age. At the 13th week of age, the functional activity of the nucleus accumbens (NAC) dopaminergic system was studied by means of transversal microdialysis. Neither Pb treatment regimen modified dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) extracellular concentrations, with respect to control rats. However, neuronal depolarisation, induced by perfusion with 60 mM KCl, increased extracellular DA levels to a significantly minor degree in rats exposed to Pb during the intrauterine life, with respect to both control and adult Pb treated rats. The in utero treated rats also responded with a lower DA release to amphetamine (1 mg/kg ip) administration. On the other hand, no difference in NAC DA level was found amongst treatment groups in response to different concentrations of the D(2)-D(3) dopaminergic agonist quinpirole, locally administered by means of inverse dialysis. These data indicate a preferential impairment of NAC DA synthesis and/or release in rats exposed to Pb acetate during their intrauterine life.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Evidence for co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex.

The aim of this study was to determine whether extracellular dopamine (DA) in the prefrontal cortex (PFC) might originate other than from DA neurons, also from noradrenergic (NA) ones. To this aim, we compared the levels of DA and NA in the dialysates from the PFC, a cortical area innervated by NA and DA neurons, and cortices that receive NA but minor or no DA projections such as the primary motor, the occipital-retrosplenial, and the cerebellar cortex. Moreover, the effect of alpha(2)-ligands and D(2)-ligands that distinctly modify NA and DA neuronal activity on extracellular NA and DA in these areas was studied. Extracellular NA concentrations were found to be similar in the different cortices, as expected from the homogeneous NA innervation, however, unexpectedly, also DA concentrations in the PFC were not significantly different from those in the other cortices. The alpha(2)-adrenoceptor agonist clonidine, intraperitoneally (i.p.) injected or locally perfused into the PFC, reduced not only extracellular NA levels, as expected from its ability to inhibit NA neuron activity, but also markedly reduced extracellular DA levels. Conversely, the alpha(2)-adrenoceptor antagonist idazoxan, i.p. injected or locally perfused into the PFC, not only increased extracellular NA levels, in line with its ability to activate NA neuron activity, but also increased those of DA. Conversely, in contrast to its ability to inhibit DA neuronal activity, the D(2) receptor agonist quinpirole only modestly and transiently reduced extracellular DA levels, while gamma-butyrolactone failed to modify DA levels in the PFC; conversely, haloperidol, at variance from its ability to activate DA neurons, failed to significantly modify extracellular DA levels in the PFC. Both haloperidol and quinpirole were totally ineffective after local perfusion into the PFC. Systemically injected or locally perfused, clonidine and idazoxan also modified both DA and NA concentrations in dialysates from primary motor, occipital-retrosplenial and cerebellar cortices as observed in the PFC. Finally, i.p. injected or locally perfused, clonidine reduced and idazoxan increased extracellular NA levels in the caudate nucleus, but neither alpha(2)-ligand significantly modified extracellular DA levels. Our results suggest that extracellular DA in the PFC, as well as in the other cortices, may depend on NA rather than DA innervation and activity. They suggest that dialysate DA reflects the amine released from NA neurons as well, where DA acts not only as NA precursor but also as co-transmitter. The co-release of NA and DA seems to be controlled by alpha(2)-receptors located on NA nerve terminals.

4-Butyrolactone↗
PubMed2000

Chronic lithium chloride fails to prevent imipramine-induced sensitization to the dopamine D(2)-like receptor agonist quinpirole.

Lithium salts, an effective antimanic treatment, are able to prevent the development of the dopaminergic behavioural supersensitivity induced by chronic treatment with neuroleptics, by denervation of the dopaminergic terminal fields and by rapid eye movements (REM) sleep deprivation, which is considered a model of mania. We have studied the effect of a lithium (LiCl) diet, inducing a lithium serum level in the range of therapeutic efficacy, on the development of the supersensitivity to the locomotor effect of the dopamine D(2)-like receptor agonist, quinpirole, induced by chronic treatment with the antidepressant drug, imipramine. The results show that lithium is not able to prevent the development of such behavioural supersensitivity. The present data suggest that antidepressant-induced dopaminergic supersensitivity might provide a useful model of those manic states induced by (or subsequent to) antidepressant treatments. Moreover, the finding is consistent with the view that antidepressant-induced dopaminergic supersensitivity might play a role in the therapeutic effect of these drugs (which is known to be augmented by lithium, and not antagonised). Finally, the results show that the dopaminergic supersensitivity induced by imipramine is qualitatively different from that induced by neuroleptics or denervation of the dopaminergic terminal fields.

Analysis of Variance↗
PubMed2000

Dissociation of haloperidol, clozapine, and olanzapine effects on electrical activity of mesocortical dopamine neurons and dopamine release in the prefrontal cortex.

The aim of the present study was to compare the effects of the typical antipsychotic haloperidol and the atypical antipsychotics clozapine and olanzapine on both extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) as well as electrical activity of mesoprefrontal DA (mPFC-DA) neurons. Extracellular single unit recordings and microdialysis experiments were carried out in different groups of chloral hydrate anesthetised rats under identical experimental conditions. Intravenous administration of haloperidol, clozapine, and olanzapine increased the firing rate and burst activity of antidromically-identified mPFC-DA neurons; maximal increase in firing rate of approximately 140, 155, and 70 %, was produced by haloperidol, clozapine, and olanzapine at doses of 0.2, 2.5, and 1 mg/kg, i.v., respectively. Intravenous administration of the same doses increased extracellular DA levels in mPFC by 20%, 190%, and 70%, respectively. Moreover, while haloperidol and olanzapine increased extracellular levels of the deaminated DA metabolite DOPAC, by 60% and 40%, respectively, clozapine was totally ineffective. The D1 receptor antagonist SCH 23390 modified neither DA output nor neuronal firing. To determine whether the effect of the three antipsychotics on DA release might depend on a direct action on the mPFC, rats were perfused locally via inverse dialysis in the mPFC at concentrations ranging from 10(-6) to 10(-4)M. While clozapine and olanzapine increased extracellular DA concentrations by up to 400% of basal level, haloperidol was totally ineffective. The results obtained from this study indicate that the rank potency of the three antipsychotics in stimulating the firing rate of DA neurons projecting to mPFC, correlates with their affinity for D2 receptors and doses used clinically. On the other hand, their stimulating effect on DA release does not correlate with their effect on neuronal firing but depends on a direct action on the mPFC.

Action Potentials↗
PubMed1997

Behavioural sensitization of mesolimbic dopamine D2 receptors in chronic fluoxetine-treated rats.

A common action of chronic antidepressant treatments is the potentiation of dopaminergic transmission in the limbic system. We now report that chronic, but not acute, treatment with fluoxetine (2.5 mg/kg by intragastric gavage once a day for 21 days) potentiates the locomotor stimulant effect of quinpirole, a selective dopamine D2/D3 receptor agonist. However, neither quinpirole-induced stereotypies nor the sedative effects elicited by low doses of this dopamine receptor agonist are influenced by chronic fluoxetine. These results suggest that fluoxetine, as well as classical antidepressants, sensitize postsynaptic dopamine D2/D3 receptors in the mesolimbic system.

Animals↗
PubMed1996

Disulfiram and diethyldithiocarbamate intoxication affects the storage and release of striatal dopamine.

Acute intoxication and chronic therapy with the alcohol consumption deterrent dithiocarbamate disulfiram have been associated with several neurological complications perhaps involving the impairment of neurotransmitter pathways. In this study we have tested the hypothesis that dopaminergic malfunction is a critical component in disulfiram-evoked neurotoxicity. Disulfiram antagonized the in vitro striatal binding of [3H]tyramine, a putative marker of the vesicular transporter for dopamine, and the uptake of [3H]dopamine into striatal synaptic vesicles, with inhibitory constants (Ki) in the range of reported blood dithiocarbamate levels in treated alcoholics. Furthermore, disulfiram provoked a loss of radioactivity from [3H]dopamine-preloaded striatal vesicles, when added directly to the incubation mixture. Several metal-containing fungicide analogs were also potent displacers of specifically bound [3H]tyramine. Diethyldithiocarbamate (DDC), the major metabolite of disulfiram, had none of these effects. The intraperitoneal injection of a high dose of disulfiram and DDC into rats, mimicking acute intoxication, induced in vivo overflow of striatal dopamine from both a reserpine-sensitive (vesicular) and an alpha-methyl-p-tyrosine-sensitive (cytoplasmic) pool. The vesicular component of in vivo dopamine release resulted mainly from a direct activity of disulfiram, on the organelles (interaction with the carrier for dopamine plus membrane permeabilization) and indirectly through the mediation of serotonergic 5-HT3 receptors. DDC acted poorly at the vesicle membrane, and the in vivo releasing effect of dopamine was only partially prevented by the inhibition of 5-HT3 receptors, thus suggesting the role of additional mechanisms. It is concluded that disulfiram intoxication may acutely disrupt dopamine balance, an effect probably underlying some of the central neurotoxic, extrapyramidal symptoms associated with dithiocarbamate overdose.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Biochemical and electrophysiological effects of 7-OH-DPAT on the mesolimbic dopaminergic system.

Systemic administration of the putative selective D3 receptor agonist 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) consistently decreased extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and dopaminergic neuronal activity in the ventral tegmental area. 7-OH-DPAT inhibited dopamine release in the nucleus accumbens also when locally perfused through the dialysis probe. The results suggest the possibility that stimulation of dopamine D3 receptors with 7-OH-DPAT mimic biochemical and electrophysiological actions previously ascribed to D2 autoreceptor stimulation; however the lack of selective D3 antagonist precludes any firm conclusion in this sense.

Animals↗
PubMed1994

Naloxone antagonizes ethanol- but not gamma-hydroxybutyrate-induced sleep in mice.

The present study examined the effect of naloxone on ethanol- and gamma-hydroxybutyric acid-induced narcosis in mice and the changes induced by these drugs on striatal dopamine metabolism. The results show that naloxone (1-10 mg/kg s.c.) markedly reduced ethanol-induced narcosis but failed to modify the duration of sleep induced by gamma-hydroxybutyrate. Naloxone (10 mg/kg) modified neither ethanol- nor gamma-hydroxybutyrate-induced changes in striatal dopamine and dihydroxyphenylacetic acid (DOPAC) content. The results suggest that gamma-hydroxybutyrate- and ethanol-induced narcosis are mediated by different mechanisms and that opioid receptors are not involved in the changes in dopamine metabolism induced by these compounds.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Effect of ethanol on extracellular 5-hydroxytryptamine output in rat frontal cortex.

The effect of acute administration of ethanol on the release of 5-hydroxytryptamine (5-HT) in the frontal cortex of "Sardinian alcohol preferring" rats, "Sardinian non-preferring" rats and control rats was investigated using in vivo microdialysis. At the dosage of 2.5 g/kg i.p. ethanol increased the level of 5-HT in the dialysate by approximately 80 +/- 20% of basal values in the Sardinian alcohol preferring rats whereas no effect was observed in Sardinian non-preferring and control rats.

Animals↗
PubMed1992

Failure by tricyclic antidepressants to affect the increase of dopamine extracellular concentrations produced by haloperidol in the caudate and accumbens nuclei of rats.

The effect of different inhibitors of monoamine uptake on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) neuronal outflow was studied in the caudate and accumbens nuclei of rats, using the in vivo brain microdialysis method coupled to HPLC electrochemical detection. Under conditions of DA receptor blockade (as produced by the i.p. administration of 0.25 mg/kg of haloperidol), cocaine, GBR-12909 and d-amphetamine increased the concentration of extracellular DA beyond the effect produced by haloperidol alone in both areas studied. GBR-12909 and cocaine also increased DOPAC concentration, while d-amphetamine decreased it. On the contrary, the tricyclic antidepressants (TCA), desipramine and chloripramine, failed to modify the effect of haloperidol on DA and DOPAC neuronal outflow. It was concluded that: (a) nonadrenergic and serotonergic nerve terminals do not take up DA released from dopaminergic neurons, and (b) TCA have no effect on dopaminergic terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

NMDA receptor inhibition prevents tolerance to cocaine.

Male rats were treated with cocaine by utilizing two different experimental paradigms. One group of animals received a low dose (10 mg/kg, IP) of cocaine for 7 days. A second group received 40 mg/kg IP of cocaine for 3 days. In both experimental groups, half the animals were concomitantly treated with 0.25 mg/kg IP (+)-5methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10- imine maleate (MK-801), a noncompetitive NMDA receptor antagonist. Rats treated with the low dose of cocaine after 7 days developed tolerance to the stimulation of locomotor activity induced by cocaine and by the dopamine D2 agonist quinpirole. Rats treated with 40 mg/kg of cocaine showed a marked behavioral sensitization. Both these effects, tolerance and sensitization, were prevented by coadministration of MK-801, thus suggesting these two phenomena are different aspects of a common neuronal response in which NMDA transmission plays a crucial role.

Animals↗
PubMed1991

Inhibition of [3H]dopamine uptake by flunarizine.

The effect of different calcium channel blockers was studied on basal and cocaine-inhibited [3H]dopamine uptake in rat striatal synaptosomes. Isradipine (dihydropyridine calcium antagonist) and diltiazem (L-type calcium antagonist) were devoid of effect on [3H]dopamine uptake, while flunarizine (T-type calcium antagonist) inhibited [3H]dopamine uptake. Flunarizine inhibition was competitive and the inhibitory curve was biphasic with a Hill coefficient of 2.1. The high Hill number suggested a mechanism of positive cooperativity between two sites. Flunarizine inhibition showed a complex interaction with cocaine inhibition. While flunarizine at low concentrations interacts with a distinct site, at higher concentrations it interacts with the same site as cocaine. The relevance of this finding for the potentiation by flunarizine of cocaine-induced dopamine release in vivo is discussed.

Animals↗
PubMed1990

Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rats displayed particular behaviour characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behaviour was potently antagonized by the administration of the D1-selective antagonist SCH 23390. In this paper we show that concomitantly to this behaviour, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. These data suggest an active role of limbic D1 receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.

Adenylyl Cyclases↗
PubMed1990

Central dopaminergic transmission is selectively increased in the limbic system of rats chronically exposed to antidepressants.

Repeated electroconvulsive shock (ECS) exposure produced a decrease of [3H]SCH 23390 binding sites and a reduced response of adenylate cyclase activity to dopamine D-1 receptor stimulation in the rat limbic area analogous to that previously observed in rats chronically treated with imipramine. These effects were completely prevented by the repeated administration of a small dose of alpha-methyl-p-tyrosine (alpha-MPT), associated with the tricyclic compound. Increased dopaminergic transmission seems to be involved in the mechanism of antidepressant action. Rats chronically treated with imipramine showed a decrease of dihydroxyphenylacetic acid (DOPAC) concentration restricted to the limbic area. Finally, both imipramine and desipramine blocked the uptake of [3H]dopamine in the limbic system with a 100-fold greater potency than that observed in the basal ganglia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Selective adenylate cyclase increase in the limbic area of long-term imipramine-treated rats.

Long-term administration of imipramine to rats produced an increase in the Vmax of forskolin- or guanylylimidodiphosphate (Gpp(NH))p-activated adenylate cyclase only in the limbic area. This effect was prevented by the daily administration of alpha-methyl-p-tyrosine (alpha-MPT), given together with imipramine, at a dose (50 mg/kg) which had no effect on adenylate cyclase activity per se. The time course of the effects of chronic imipramine on dopaminergic transmission in the limbic area showed that the decrease in both D-1 receptor number and adenylate cyclase stimulation by dopamine (DA) reached significance on day 8 of treatment and were maximal on day 15. The Vmax of the enzyme started to increase on day 15 and was further increased on day 21. Possible mechanisms underlying these effects are discussed.

Adenylyl Cyclases↗
PubMed1989

Chronic imipramine reduces [3H]SCH 23390 binding and DA-sensitive adenylate cyclase in the limbic system.

[3H]SCH 23390 binding and dopamine (DA)-stimulated adenylate cyclase activity were measured in brain membrane preparations from rats chronically treated with imipramine (10 mg/kg twice daily for 14 days). [3H]SCH 23390 binding sites were decreased by 27% in the limbic system but only 14% in the striatum. The responsiveness of adenylate cyclase to DA was reduced by 38% in the limbic system but was not modified in the striatum. Concomitant treatment with alpha-methyltyrosine (alpha-MPT) (50 mg/kg daily for 14 days) prevented the imipramine-induced reduction in both [3H]SCH 23390 binding sites and the responsiveness of adenylate cyclase to DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Resistance to extrapyramidal effects of opiates in rats chronically treated with SCH 23390.

Rats made tolerant to morphine show neither a change in brain opiate receptor number nor altered sensitivity to the inhibitory effect of opiates on striatal adenylate cyclase (AC) activity. Interestingly, SCH 23390, a selective blocker of D1 dopamine (DA) receptors which, given chronically to rats, induces a 32% increase in D1 receptor number and increases the Vmax of D1-stimulated striatal AC, resulted in marked resistance to acute morphine effects. In particular, rats chronically treated with SCH 23390 failed to show muscular rigidity and increased striatal dihydroxyphenylacetic acid (DOPAC) concentration after morphine. Moreover, basal striatal AC activity in these animals had a significantly reduced sensitivity to opiate inhibition. On the other hand, decreased AC sensitivity to acetylcholine (ACh) inhibition observed in the striatum of rats chronically treated with DFP, an irreversible blocker of acetylcholinesterase, appeared to be secondary to the downregulation of muscarinic receptors and thus did not modify the opiate inhibitory capacity. It was concluded that although a potentiation of striatal AC impairs opiate action, such mechanism is not involved in morphine tolerance.

3,4-Dihydroxyphenylacetic Acid↗