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1

Emission of 50‑kHz ultrasonic vocalizations in dopamine-denervated rats treated with amphetamine: relevance to neurocircuitries involved in drug-mediated reward

100%
Costa G., Marongiu J., Morelli M., Simola N.
Acta Neurobiologiae Experimentalis
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2019
|
tom 79
|
nr Suppl.1
Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to pleasurable stimuli, and USVs are increasingly being used to investigate the affective properties of drugs. Dopamine in the shell of the nucleus accumbens is instrumental in the emission of 50-kHz USVs, but little is known about how calling behavior is modulated by other brain regions that receive dopaminergic innervation. To clarify this issue, we evaluated calling behavior stimulated by repeated amphetamine administration in rats subjected to either bilateral or unilateral dopaminergic denervation with 6‑OHDA in the medial prefrontal cortex (mPFC), dorsolateral striatum (DLS), or medial forebrain bundle (MFB). Dopaminergic denervation in the PFC, DLS, or MFB only partially attenuated the development of 50-kHz USVs sensitization during repeated treatment with amphetamine. However, rats bearing a dopaminergic denervation in the mPFC emitted a low number of conditioned USVs upon re-exposure to the amphetamine-paired environment. Sensitization in ultrasonic calling and emission of 50-kHz USVs conditioned to an environment previously paired with drug administration have recently emerged as behavioral correlates of the motivational properties of drugs of abuse. Accordingly, the present results may provide new insight into the neurocircuitries involved in reward and motivation mediated by addictive drugs.
2

A2A adenosine receptor antagonists effet on hydroxyl radical generation in DA depleted striatum with reserpine

100%
Golembiowska K., Dziubina A., Morelli M.
Acta Neurobiologiae Experimentalis
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2009
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tom 69
|
nr 3
Although the cause of DA neurons neurodegeneration is still unknown, oxidative stress is paramount in the pathogenesis of Parkinson’s disease. An accumulation of cytosolic DA has been shown to be neurotoxic through the generation of free radicals (FR). Searching for FR scavengers, we studied the effect of selective A2A adenosine receptor antagonists, shown to have neuroprotective properties, on hydroxyl radical (HR) production in rat striatum with reserpine impaired DA storage. We found an increase in extracellular glutamate and HR levels in DA-depleted striatum. CSC (1 mg/kg), ZM 241385 (3 mg/ kg) and L-DOPA (25 mg/kg) normalized glutamate release and combination of A2A antagonists and L-DOPA showed similar effect. CSC increased DA and HR levels but ZM 241385 given alone did not affect DA nor HR levels. L-DOPA enhanced DA extracellular level but did not change the production of HR. Combination of L-DOPA and CSC further elevated DA extracellular level and markedly increased HR production while combination of L-DOPA and ZM 241385 attenuated, enhanced by L-DOPA DA level and had no effect on HR production. This data suggests that disrupted balance between DA and glutamate in DA depleted nigrostriatal neurons results in generation of neurotoxic HR. Both A2A antagonists, like L-DOPA, redress the DA/glutamate balance. However, A2A antagonists in combination with L-DOPA show different pharmacological profi le in their effect on DA release and subsequent generation of HR.
3

Priming of rotational behavior by a dopamine receptor agonist in hemiparkinsonian rats: movement-dependent induction

88%
Simola M., Di Chiara G., Daniels W., Schallert T., Morelli M.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
Repetitive stimulation of basal ganglia dopamine receptors leads to abnormal motor responses in dopamine-denervated rats. To study whether such responses were infl uenced by the previous execution of movement, we evaluated how “priming”, a phenomenon mimicking an abnormal motor response, depends on movement performance. To this end, unilaterally 6-hydroxydopamine-lesioned rats received apomorphine (0.2 mg/kg s.c.), being either allowed to move or immobilized (1 h) before, concomitantly to, or after its administration. Three days later, the dopamine D1 receptor agonist SKF 38393 (3 mg/kg s.c.) was administered. Rats that had rotated following apomorphine showed contraversive rotational behavior following SKF 38393, whilst rats that had been immobilized concomitantly to apomorphine, but neither before nor after, did not. To clarify whether immobiliztion-related stress infl uenced the results, additional rats received apomorphine plus immobilization and the corticosterone-synthesis inhibitor metyrapone (100 mg/ kg i.p.), or apomorphine plus a tail stressor, being not immobilized. Metyrapone did not affect the prevention of priming by immobilization, and tail stressor did not affect priming magnitude, suggesting that stress has minimal effect on the results observed. This study demonstrates how movement performance following initial dopaminergic stimulation governs the occurrence of an abnormal motor response to a subsequent dopaminergic challenge in dopamine-denervated rats.
4

Chronic intraventricular infusion of MPP+ with alzet osmotic minipumps in rats as a model of parkinson's disease

76%
Kuter K., Kolasiewicz W., Zapala M., Kowalska M., Golembiowska K., Morelli M., Wardas J.
Acta Neurobiologiae Experimentalis
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2009
|
tom 69
|
nr 3
An underlying mechanism of degeneration in Parkinson’s disease (PD) is unknown. The animal models of PD, developed so far have certain disadvantages; hence a search for a new model of PD seems necessary. Chronic, unilateral, intraventricular delivery of MPP+ (0.284 and 0.428 mg/kg/day for 28 days) using an ALZET osmotic minipump, implanted s.c., produced a marked, dose-dependent loss of DA and its metabolites DOPAC and HVA (50–90%) in the striatum, ipsilateral to the infusion site. DA concentration was normal in the non-infused, right striatum. Also no changes in the 5-HT level were observed. The stereological counting of the number of dopaminergic neurons in the substantia nigra pars compacta (SNc), stained with the antibody against tyrosine hydroxylase, showed their 30–50% loss on the lesioned side. Those changes were accompanied with a diminished expression of mRNA for the dopamine transporter in the SNc (by ca. 30%). Additionally, in situ hybridization studies indicated an enhanced expression of mRNA for both adenosine A2A and dopamine D2 receptors in the striatum and diminished expression of mRNA for BDNF in the hippocampus. The obtained results showed that this chronic model of continuous, intracerebral infusion of MPP+ , produced a selective nigrostriatal DA cell loss and number of other neurochemical changes resembling PD. Study supported by the grant No. NN401 1137 33 (MS&HE) and by a statutory fund from the Institute of Pharmacology, PAS, Poland.
5

Dopamine and adenosine receptor interaetion as basis for the treatment of Parkinson's disease

76%
Morelli M., Carla A. M., Simola A., Tronci E., Pontis S., Pinna A.
Acta Neurobiologiae Experimentalis
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2005
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tom 65
|
nr 3
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